| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Prepair 1000+ v1.2148 | BRIP1 | Zornitza Stark Phenotypes for gene: BRIP1 were changed from Fanconi Anaemia to Fanconi Anaemia, complementation group J, MIM# 609054 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.2146 | BRIP1 | Zornitza Stark edited their review of gene: BRIP1: Added comment: Consider for inclusion in V3 together with all FA genes.; Changed rating: RED; Changed phenotypes: Fanconi Anaemia, complementation group J, MIM# 609054; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.2045 | PET100 | Zornitza Stark Phenotypes for gene: PET100 were changed from Mitochondrial complex IV deficiency, 220110 (3) to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.2044 | PET100 | Zornitza Stark reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.2025 | NUBPL | Zornitza Stark Phenotypes for gene: NUBPL were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 21, MIM#618242 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.2021 | NDUFV2 | Zornitza Stark Phenotypes for gene: NDUFV2 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 7, MIM#618229, MONDO:0044970 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.2019 | NDUFS4 | Zornitza Stark Phenotypes for gene: NDUFS4 were changed from Leigh syndrome, 256000 (3) to Mitochondrial complex I deficiency, nuclear type 1, MIM#252010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1906 | FANCL | Zornitza Stark Phenotypes for gene: FANCL were changed from Fanconi anemia, complementation group L, 614083 (3) to Fanconi anaemia, complementation group L MIM#614083 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1904 | FANCD2 | Zornitza Stark Phenotypes for gene: FANCD2 were changed from Fanconi anemia, complementation group D2, 227646 (3) to Fanconi anaemia, complementation group D2 MIM#227646 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1902 | ERCC4 | Zornitza Stark Phenotypes for gene: ERCC4 were changed from Fanconi anemia, complementation group Q, 615272 (3) to Fanconi anemia, complementation group Q, MIM# 615272 MONDO:0014108; Xeroderma pigmentosum, group F, MIM# 278760 MONDO:0010215; XFE progeroid syndrome, MIM# 610965 MONDO:0012590 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1901 | ERCC4 | Zornitza Stark reviewed gene: ERCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group Q, MIM# 615272 MONDO:0014108, Xeroderma pigmentosum, group F, MIM# 278760 MONDO:0010215, XFE progeroid syndrome, MIM# 610965 MONDO:0012590; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1868 | NUBPL | Cassandra Muller reviewed gene: NUBPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 20818383, 32518176, 23553477, 31917109, 32518176, 31787496, 30897263, 22826544; Phenotypes: Mitochondrial complex I deficiency, nuclear type 21, 618242 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1868 | NDUFS4 | Cassandra Muller reviewed gene: NDUFS4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 1, 252010 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1868 | SEC23A |
Melanie Marty changed review comment from: SEC23A is an essential component of coat protein complex II (COPII)-coated vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex. Boyadjiev et al 2006 (PMID:16980979): One family was reported with a homozygous missense variant and craniolenticulosutural dysplasia (CLSD), with some functional studies supporting pathogenicity. Boyadjiev et al 2011 (PMID: 21039434): The same authors as above later reported another individual with similar phenotype with a paternally inherited heterozygous missense variant, this variant has 91 hets in gnomAD and the father was unaffected. They suggest digenic inheritance but found no other variants in 3 candidate genes. Wang et al 2023 (PMID: 37828500): 2 x compound heterozygous missense variants were identified in a patient with CLSD. Cisarova et al 2022 (PMID: 34580982) 1 x patient with het missense variant inherited from his affected father. Shown to be de novo in the father. Minale et al 2024 (PMID: 38275611): 1 x patient with de novo het missense variant Zebrafish models lend some support to the gene-disease association (PMID:16980979, 16980978) Summary: 2 reports of AR inheritance, 2 reports of AD inheritance, 1 uncertain; to: SEC23A is an essential component of coat protein complex II (COPII)-coated vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex. Boyadjiev et al 2006 (PMID:16980979): One family was reported with a homozygous missense variant and craniolenticulosutural dysplasia (CLSD), with some functional studies supporting pathogenicity. Boyadjiev et al 2011 (PMID: 21039434): The same authors as above later reported another individual with similar phenotype with a paternally inherited heterozygous missense variant, this variant has 91 hets in gnomAD and the father was unaffected. They suggest digenic inheritance but found no other variants in 3 candidate genes. Wang et al 2023 (PMID: 37828500): 2 x compound heterozygous missense variants were identified in a patient with CLSD. Cisarova et al 2022 (PMID: 34580982) 1 x patient with CLSD and a het missense variant inherited from his affected father. Shown to be de novo in the father. Minale et al 2024 (PMID: 38275611): 1 x patient with CLSD and a de novo het missense variant Zebrafish models lend some support to the gene-disease association (PMID:16980979, 16980978) Summary: 2 reports of AR inheritance, 2 reports of AD inheritance, 1 uncertain |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1868 | FTSJ1 | Andrew Coventry reviewed gene: FTSJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15342698, 18081026, 15162322, 26310293; Phenotypes: Intellectual developmental disorder, X-linked 9 MIM#309549, X-linked complex neurodevelopmental disorder MONDO:0100148; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1868 | FANCL | Andrew Coventry reviewed gene: FANCL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19405097, 25754594, 33394227, 33224012, 12973351, 31513304; Phenotypes: Fanconi anemia, complementation group L MIM#614083; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1868 | FANCD2 | Andrew Coventry reviewed gene: FANCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301575, 17436244, 25703294, 23613520; Phenotypes: Fanconi anemia, complementation group D2 MIM#227646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1868 | NDUFV2 | Karina Sandoval reviewed gene: NDUFV2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33811136, 34405929, 12754703, 26008862, 30770271, 19167255; Phenotypes: Mitochondrial complex I deficiency, nuclear type 7, MIM#618229, MONDO:0044970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1811 | SCO1 |
Andrew Coventry changed review comment from: Four unrelated families reported, typically presenting with lactatic acidosis and encephalopathy in infancy. SCO1 pathogenic variants were first described in an infant with respiratory distress, metabolic acidosis, hepatic failure, and encephalopathy in the setting of profound complex IV deficiency in muscle and liver. Further reports have shown phenotypic spectrum to include cardiomyopathy, encephalopathy, and lactic acidosis without cardiac or hepatic involvement. Many cases are fatal in the first few months of life. Functional studies and model organisms also present. ClinGen: While various names have been given to the constellation of features seen in those with SCO1-related disease, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the SCO1 phenotype has been lumped into one disease entity. Sources: Literature; to: Six unrelated families reported. Typically presenting with lactatic acidosis and encephalopathy in infancy. SCO1 pathogenic variants were first described in an infant with respiratory distress, metabolic acidosis, hepatic failure, and encephalopathy in the setting of profound complex IV deficiency in muscle and liver. Further reports have shown phenotypic spectrum to include cardiomyopathy, encephalopathy, and lactic acidosis without cardiac or hepatic involvement. Many cases are fatal in the first few months of life. Functional studies and model organisms also present. ClinGen: While various names have been given to the constellation of features seen in those with SCO1-related disease, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the SCO1 phenotype has been lumped into one disease entity. PMID: 39214134: 3 cases from 2 unrelated families, with developmental and epileptic encephalopathy, hypopituitarism. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1811 | SCO1 |
Andrew Coventry gene: SCO1 was added gene: SCO1 was added to Prepair 1000+. Sources: Literature Mode of inheritance for gene: SCO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCO1 were set to 11013136; 19295170; 31352446; 23878101 Phenotypes for gene: SCO1 were set to Mitochondrial disease MONDO:0044970; Mitochondrial complex IV deficiency, nuclear type 4 MIM#619048 Review for gene: SCO1 was set to GREEN Added comment: Four unrelated families reported, typically presenting with lactatic acidosis and encephalopathy in infancy. SCO1 pathogenic variants were first described in an infant with respiratory distress, metabolic acidosis, hepatic failure, and encephalopathy in the setting of profound complex IV deficiency in muscle and liver. Further reports have shown phenotypic spectrum to include cardiomyopathy, encephalopathy, and lactic acidosis without cardiac or hepatic involvement. Many cases are fatal in the first few months of life. Functional studies and model organisms also present. ClinGen: While various names have been given to the constellation of features seen in those with SCO1-related disease, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the SCO1 phenotype has been lumped into one disease entity. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1811 | PDHX |
Andrew Coventry gene: PDHX was added gene: PDHX was added to Prepair 1000+. Sources: Literature Mode of inheritance for gene: PDHX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDHX were set to 20002125; 34873726; 33092611; 30981218; 25087164; 22766002; 12557299; 14518830; 15303005; 16566017; 27343776 Phenotypes for gene: PDHX were set to Lacticacidemia due to PDX1 deficiency MIM#245349; Mitochondrial disease MONDO:0044970 Review for gene: PDHX was set to GREEN Added comment: Established gene-disease association. Clingen definitive for mitochondrial disease: "While various names have been given to the constellation of features seen in those with PDHX-related disorders, including pyruvate dehydrogenase complex deficiency or PDCD, pathogenic variants in this gene ultimately cause a primary mitochondrial disease. Therefore, the PDHX phenotype has been lumped into one disease entity according to the ClinGen Lumping and Splitting Framework." Condition is a metabolic disorder associated with abnormal function of the mitochondria in cells, thus depriving the body of energy. Progressive neurological symptoms usually start in infancy but may be evident at birth, or in later childhood; these symptoms may include developmental delay, intermittent ataxia, poor muscle tone (hypotonia), abnormal eye movements, or seizures. Severe lethargy, poor feeding, and tachypnea (rapid breathing) commonly occur, especially during times of illness, stress, or high carbohydrate intake. Clingen: Age of onset ranges from the first days of life to later in childhood, with some individuals living well into adulthood. Clinical features in affected individuals include neonatal lactic acidosis, LSS, seizures, spasticity, agenesis of the corpus callosum, cerebral atrophy, vomiting, and optic atrophy. Note: PDHX c.1336C>T (p.Arg446Ter) is a Roma founder variant; c.1182+2T>C (p.Ile386SerfsTer13) is a Moroccan founder variant. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1710 | PLEC | Zornitza Stark Phenotypes for gene: PLEC were changed from Epidermolysis bullosa simplex with pyloric atresia, 612138 (3) to Epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive, MIM# 616487; Epidermolysis bullosa simplex 5B, with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex 5C, with pyloric atresia MIM# 612138; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1688 | NYX | Zornitza Stark Phenotypes for gene: NYX were changed from Night blindness, congenital stationary (complete), 1A, X-linked, MIM #310500 to Night blindness, congenital stationary (complete), 1A, X-linked MIM310500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1674 | NDUFS1 | Zornitza Stark Phenotypes for gene: NDUFS1 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 5, MIM#618226 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1670 | MPLKIP | Zornitza Stark Marked gene: MPLKIP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1670 | MPLKIP | Zornitza Stark Gene: mplkip has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1670 | MPLKIP | Zornitza Stark Phenotypes for gene: MPLKIP were changed from Trichothiodystrophy 4, nonphotosensitive, 234050 (3) to Trichothiodystrophy 4, nonphotosensitive MIM#234050 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1669 | MPLKIP | Zornitza Stark Publications for gene: MPLKIP were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1668 | MMAB | Zornitza Stark Phenotypes for gene: MMAB were changed from Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type, 251110 (3) to Methylmalonic aciduria, vitamin B12-responsive, cblB type MIM#251110 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1589 | GPR179 | Lilian Downie Phenotypes for gene: GPR179 were changed from Night blindness, congenital stationary (complete), 1E, autosomal recessive, 614565 (3) to GPR179-related retinopathy (MONDO:0800396) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1568 | APC2 |
Andrew Coventry gene: APC2 was added gene: APC2 was added to Prepair 1000+. Sources: Literature Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: APC2 were set to 31585108 Phenotypes for gene: APC2 were set to Cortical dysplasia, complex, with other brain malformations 10 MIM#618677; Intellectual developmental disorder, autosomal recessive 74 MIM#617169; Lissencephaly spectrum disorders MONDO:0018838 Review for gene: APC2 was set to GREEN Added comment: 12 individuals from 8 unrelated families; intellectual disability, seizures, cortical dysplasia including posterior to anterior predominant pattern of lissencephaly, heterotopias, paucity of white matter, thin corpus callosum. Definitive classification by ClinGen. Mouse model present. Note: Gene has also been implicated in Sotos Syndrome Type 3 which features intellectual disability and characteristic facial features Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1568 | GPR179 | Karina Sandoval reviewed gene: GPR179: Rating: GREEN; Mode of pathogenicity: None; Publications: 22325361; Phenotypes: Night blindness, congenital stationary (complete), 1E, autosomal recessive, MIM#614565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1568 | FANCA | Melanie Marty reviewed gene: FANCA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group A, MIM# 227650, MONDO:0009215; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1566 | PLEC |
Lauren Thomas changed review comment from: PLEC was first reported in relation to autosomal recessive limb-girdle muscular dystrophy which is typically characterized by early childhood onset of proximal muscle weakness and atrophy, notably without skin involvement. PLEC has also been noted to be associated with epidermolysis bullosa 5A-5D. ClinGen: The molecular mechanisms underlying EBS with muscular dystrophy (EBS5B) has primarily been nonsense, out-of-frame insertions or deletions within exon 31 and 32, leading to premature protein termination. The mechanism underlying autosomal recessive limb-girdle muscular dystrophy appears to be recessive truncating variants in exon 1f. HGNC approved symbol/name: PLEC Is the phenotype(s) severe and onset <18yo? Yes Known technical challenges? For AR limb-girdle muscular dystrophy, a 9-bp deletion has been reported in seven probands in two publications (PMIDs: 21109228, 32605089) Gene reported in 3 independent families: Yes NOTE: AD phenotype - Epidermolysis bullosa simplex 5A, Ogna type MIM# 131950; to: PLEC was first reported in relation to autosomal recessive limb-girdle muscular dystrophy which is typically characterized by early childhood onset of proximal muscle weakness and atrophy, notably without skin involvement. PLEC has also been noted to be associated with epidermolysis bullosa 5A-5D. ClinGen: The molecular mechanisms underlying EBS with muscular dystrophy (EBS5B) has primarily been nonsense, out-of-frame insertions or deletions within exon 31 and 32, leading to premature protein termination. The mechanism underlying autosomal recessive limb-girdle muscular dystrophy appears to be recessive truncating variants in exon 1f. HGNC approved symbol/name: PLEC Is the phenotype(s) severe and onset <18yo? Yes Known technical challenges? For AR limb-girdle muscular dystrophy, a 9-bp deletion has been reported in seven probands in two publications (PMIDs: 21109228, 32605089) Gene reported in 3 independent families: Yes NOTE: AD phenotype - Epidermolysis bullosa simplex 5A, Ogna type MIM# 131950 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1566 | PLEC |
Lauren Thomas changed review comment from: PLEC was first reported in relation to autosomal recessive limb-girdle muscular dystrophy which is typically characterized by early childhood onset of proximal muscle weakness and atrophy, notably without skin involvement. PLEC has also been noted to be associated with epidermolysis bullosa 5A-5D. ClinGen: The molecular mechanisms underlying EBS with muscular dystrophy (EBS5B) has primarily been nonsense, out-of-frame insertions or deletions within exon 31 and 32, leading to premature protein termination. The mechanism underlying autosomal recessive limb-girdle muscular dystrophy appears to be recessive truncating variants in exon 1f. HGNC approved symbol/name: PLEC Is the phenotype(s) severe and onset <18yo? Yes Known technical challenges? For AR limb-girdle muscular dystrophy, a 9-bp deletion has been reported in seven probands in two publications (PMIDs: 21109228, 32605089) Gene reported in 3 independent families: Yes NOTE: AD phenotype - Epidermolysis bullosa simplex 5A, Ogna type MIM# 131950; to: PLEC was first reported in relation to autosomal recessive limb-girdle muscular dystrophy which is typically characterized by early childhood onset of proximal muscle weakness and atrophy, notably without skin involvement. PLEC has also been noted to be associated with epidermolysis bullosa 5A-5D. ClinGen: The molecular mechanisms underlying EBS with muscular dystrophy (EBS5B) has primarily been nonsense, out-of-frame insertions or deletions within exon 31 and 32, leading to premature protein termination. The mechanism underlying autosomal recessive limb-girdle muscular dystrophy appears to be recessive truncating variants in exon 1f. HGNC approved symbol/name: PLEC Is the phenotype(s) severe and onset <18yo? Yes Known technical challenges? For AR limb-girdle muscular dystrophy, a 9-bp deletion has been reported in seven probands in two publications (PMIDs: 21109228, 32605089) Gene reported in 3 independent families: Yes NOTE: AD phenotype - Epidermolysis bullosa simplex 5A, Ogna type MIM# 131950 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1566 | PLEC | Lauren Thomas reviewed gene: PLEC: Rating: GREEN; Mode of pathogenicity: None; Publications: 28447722, 25556389, 32576226; Phenotypes: Epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive, MIM# 616487, Epidermolysis bullosa simplex 5B, with muscular dystrophy, MIM# 226670, Epidermolysis bullosa simplex 5C, with pyloric atresia MIM# 612138, Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1566 | TBCK | Andrew Coventry reviewed gene: TBCK: Rating: GREEN; Mode of pathogenicity: None; Publications: 27040691, 30591081, 35095425, 36317458; Phenotypes: Syndromic complex neurodevelopmental disorder MONDO:0800439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1508 | NDUFV1 | Zornitza Stark Phenotypes for gene: NDUFV1 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1501 | KRT5 | Zornitza Stark Phenotypes for gene: KRT5 were changed from EEpidermolysis bullosa simplex 2D, generalized, intermediate or severe, autosomal recessive, MIM#619599 to Epidermolysis bullosa simplex 2D, generalized, intermediate or severe, autosomal recessive, MIM#619599 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1500 | KRT5 | Zornitza Stark Phenotypes for gene: KRT5 were changed from Epidermolysis bullosa simplex, recessive 1, 601001 (3) to EEpidermolysis bullosa simplex 2D, generalized, intermediate or severe, autosomal recessive, MIM#619599 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1459 | KRT5 | Clare Hunt reviewed gene: KRT5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31302245, 31312705, 34912369; Phenotypes: Epidermolysis bullosa simplex 2D, generalized, intermediate or severe, autosomal recessive, MIM#619599; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1459 | UQCRC2 | Lisa Norbart reviewed gene: UQCRC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28275242, 33865955, 23281071; Phenotypes: Mitochondrial complex III deficiency, nuclear type 5, MIM#615160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1459 | NDUFV1 | Lauren Thomas reviewed gene: NDUFV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34807224; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1397 | NDUFS1 | Lisa Norbart reviewed gene: NDUFS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24952175, 20797884, 15824269, 25615419, 11349233, 22399432; Phenotypes: Mitochondrial complex I deficiency, nuclear type 5, MIM#618226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1397 | MPL | Zornitza Stark Marked gene: MPL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1397 | MPL | Zornitza Stark Gene: mpl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1397 | MPL | Zornitza Stark Publications for gene: MPL were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1369 | NDUFA10 | Zornitza Stark Phenotypes for gene: NDUFA10 were changed from Leigh syndrome, 256000 (3), Autosomal recessive, Mitochondrial to Mitochondrial complex I deficiency, nuclear type 22, MIM#618243 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1367 | NDUFA10 | Lisa Norbart reviewed gene: NDUFA10: Rating: GREEN; Mode of pathogenicity: None; Publications: 21150889, 26741492, 28247337; Phenotypes: Mitochondrial complex I deficiency, nuclear type 22, MIM#618243; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1367 | MUT |
Lauren Thomas changed review comment from: Isolated methylmalonic aciduria is found in patients with mutations in the MUT gene causing partial, mut(-), or complete, mut(0), enzyme deficiency. Variable severity and age of onset: • Infantile completely deficient (mut0) or non-B12-responsive (clbB) is the most common phenotype and presents during infancy. Infants are normal at birth, but develop lethargy, vomiting, and dehydration within the first few months of life. They may also exhibit hepatomegaly, hypotonia, encephalopathy, metabolic acidosis, ketosis and ketonuria, hyperammonemia, and hyperglycemia. • Partially deficient (mut-) or B12-responsive (cblA, cblD, rarely cblB) is an intermediate phenotype that can occur in the first few months or years of life. Symptoms include feeding problems, failure to thrive, hypotonia, and developmental delay. Some have protein aversion and vomiting, and lethargy after protein intake. HGNC approved symbol/name: MMUT * Is the phenotype(s) severe and onset <18yo? Yes Treatments available: cobalamin, N-carbamylglutamate, carnitine, diet, liver transplant Known technical challenges? No Gene reported in 3 independent families: Yes * NOTE: gene previously called MUT; to: Isolated methylmalonic aciduria is found in patients with mutations in the MUT gene causing partial, mut(-), or complete, mut(0), enzyme deficiency. Variable severity and age of onset: • Infantile completely deficient (mut0) or non-B12-responsive (clbB) is the most common phenotype and presents during infancy. Infants are normal at birth, but develop lethargy, vomiting, and dehydration within the first few months of life. They may also exhibit hepatomegaly, hypotonia, encephalopathy, metabolic acidosis, ketosis and ketonuria, hyperammonemia, and hyperglycemia. • Partially deficient (mut-) or B12-responsive (cblA, cblD, rarely cblB) is an intermediate phenotype that can occur in the first few months or years of life. Symptoms include feeding problems, failure to thrive, hypotonia, and developmental delay. Some have protein aversion and vomiting, and lethargy after protein intake. HGNC approved symbol/name: MMUT * Is the phenotype(s) severe and onset <18yo? Yes Treatments available: cobalamin, N-carbamylglutamate, carnitine, diet, liver transplant Known technical challenges? No Gene reported in 3 independent families: Yes * NOTE: gene previously called MUT |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1367 | MPL | Lauren Thomas reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 17054430, 16351641, 11133753; Phenotypes: Amegakaryocytic thrombocytopenia, congenital, 1, MIM# 604498; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1318 | TTC19 | Zornitza Stark Phenotypes for gene: TTC19 were changed from Mitochondrial complex III deficiency, nuclear type 2, 615157 (3) to Mitochondrial complex III deficiency, nuclear type 2 MIM#615157 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1268 | COL7A1 |
Michelle Torres changed review comment from: The COL7A1 gene is associated with dystrophic epidermolysis bullosa (DEB), a genetic skin disorder affecting skin and nails that usually presents at birth. There are 2 main subtypes: dominant (DDEB) and recessive (RDEB), both with many clinical subtypes. For carrier screening testing, the only relevant subtypes are AR. Genotype-phenotype correlation is unclear (PMID: 31670143), but variants resulting in complete absence of protein are usually associated with the most severe RDEB (PMID: 32506467). The recessive exon skipping variants are scattered throughout the gene (PMID: 31670143). NB: Transient bullous of the newborn MIM#131705 is predominantly AD, but AR cases have been reported (PMID: 25639640 Table 1). It has onset at birth, but skin lesions resolve between 6 months and 2 years of age. Some patients have milder persistent blistering.; to: The COL7A1 gene is associated with dystrophic epidermolysis bullosa (DEB), a genetic skin disorder affecting skin and nails that usually presents at birth. There are 2 main subtypes: dominant (DDEB) and recessive (RDEB), both with many clinical subtypes. For carrier screening testing, the only relevant subtypes are AR. Genotype-phenotype correlation is unclear (PMID: 31670143), but variants resulting in complete absence of protein are usually associated with the most severe RDEB (PMID: 32506467). The recessive exon skipping variants are scattered throughout the gene (PMID: 31670143). NB: Transient bullous of the newborn MIM#131705 is predominantly AD, but AR cases have been reported (PMID: 25639640 Table 1). It has onset at birth, but skin lesions resolve between 6 months and 2 years of age. Some patients have milder persistent blistering. As noted above, genotype-phenotype correlation is unclear. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1268 | COL7A1 |
Michelle Torres changed review comment from: The COL7A1 gene is associated with dystrophic epidermolysis bullosa (DEB), a genetic skin disorder affecting skin and nails that usually presents at birth. There are 2 main subtypes: dominant (DDEB) and recessive (RDEB), both with many clinical subtypes. For carrier screening testing, the only relevant subtypes are AR. Genotype-phenotype correlation is unclear (PMID: 31670143), but variants resulting in complete absence of protein are usually associated with the most severe RDEB (PMID: 32506467). The recessive exon skipping variants are scattered throughout the gene (PMID: 31670143). NB: Transient bullous of the newborn MIM#131705 is predominantly AD, but AR cases have been reported (PMID: 25639640 Table 1). It has onset at birth, but skin lesions resolve between 6 months and 2 years of age. Some patients have milder persistent blistering. Relevance for Prepair requires discussion.; to: The COL7A1 gene is associated with dystrophic epidermolysis bullosa (DEB), a genetic skin disorder affecting skin and nails that usually presents at birth. There are 2 main subtypes: dominant (DDEB) and recessive (RDEB), both with many clinical subtypes. For carrier screening testing, the only relevant subtypes are AR. Genotype-phenotype correlation is unclear (PMID: 31670143), but variants resulting in complete absence of protein are usually associated with the most severe RDEB (PMID: 32506467). The recessive exon skipping variants are scattered throughout the gene (PMID: 31670143). NB: Transient bullous of the newborn MIM#131705 is predominantly AD, but AR cases have been reported (PMID: 25639640 Table 1). It has onset at birth, but skin lesions resolve between 6 months and 2 years of age. Some patients have milder persistent blistering. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1257 | TTC19 | Michelle Torres reviewed gene: TTC19: Rating: GREEN; Mode of pathogenicity: None; Publications: 21278747, 23532514, 24368687, 24397319, 25887401; Phenotypes: Mitochondrial complex III deficiency, nuclear type 2 MIM#615157; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1227 | NDUFS2 | Zornitza Stark Phenotypes for gene: NDUFS2 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 6, MIM #618228 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1160 | RFXANK | Zornitza Stark Phenotypes for gene: RFXANK were changed from MHC class II deficiency, complementation group B, 209920 (3) to MHC class II deficiency 2, MIM#620815 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1158 | MTR | Zornitza Stark Phenotypes for gene: MTR were changed from Homocystinuria-megaloblastic anemia, cblG complementation type, 250940 (3) to Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1154 | SDHAF1 | Zornitza Stark Phenotypes for gene: SDHAF1 were changed from Mitochondrial complex II deficiency, 252011 (3) to Mitochondrial complex II deficiency, nuclear type 2, MIM#619166 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1133 | NDUFS6 | Zornitza Stark Phenotypes for gene: NDUFS6 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 9 (MIM#618232) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1129 | CFI | Zornitza Stark Phenotypes for gene: CFI were changed from Complement factor I deficiency, 610984 (3) to Complement factor I deficiency, MIM#610984 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1060 | FANCE | Zornitza Stark Phenotypes for gene: FANCE were changed from Fanconi anemia, complementation group E, 600901 (3) to Fanconi anaemia, complementation group E, MIM#600901 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1043 | UBE2T | Zornitza Stark Phenotypes for gene: UBE2T were changed from Fanconi anemia, complementation group T, 616435 (3) to Fanconi anaemia, complementation group T, MIM#616435 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.1000 | NDUFS7 | Zornitza Stark Phenotypes for gene: NDUFS7 were changed from Leigh syndrome, 256000 (3) to Mitochondrial complex I deficiency, nuclear type 3 MIM#618224 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | NDUFS7 | Michelle Torres reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 17604671, 17275378, 10360771, 22644603; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | STIL |
Ee Ming Wong changed review comment from: - More than 10 unrelated families reported. - Onset at birth - PMID: 24485834; 29352115: Complete loss of STIL is not compatible with life. Genetic mutations in human STIL result in 1. residual expression or 2. stabilization of STIL: PTCs that delete of the critical C-terminal KEN Box domain involved in Anaphase-Promoting-Complex/Cyclosome (APC/C)-mediated degradation of STIL5 were shown to result in mutant STIL stabilization and accumulation and subsequent centriole amplification. Demonstrated for p.(Val1219X) and p.(Gln1239X), suggested gain of function.; to: - More than 10 unrelated families reported. - Onset at birth - PMID: 24485834; 29352115: Complete loss of STIL is not compatible with life. Genetic mutations in human STIL result in 1. residual expression or 2. stabilization of mutant STIL: PTCs that delete of the critical C-terminal KEN Box domain involved in Anaphase-Promoting-Complex/Cyclosome (APC/C)-mediated degradation of STIL5 were shown to result in mutant STIL stabilization and accumulation and subsequent centriole amplification. Demonstrated for p.(Val1219X) and p.(Gln1239X), suggested gain of function. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | UBE2T | Ee Ming Wong reviewed gene: UBE2T: Rating: GREEN; Mode of pathogenicity: None; Publications: 32646888, 26119737, 26046368, 26085575; Phenotypes: Fanconi anemia, complementation group T (MIM#616435); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | TBX22 |
Ee Ming Wong changed review comment from: 1. Cleft palate with ankyloglossia (MIM# 303400) - More than 10 families reported with cleft palate/ankyloglossia and variants in this gene. - PMID:36901693 - Characterised by a cleft palate phenotype that is most often present in males and ranges from a high-arched palate, bifid uvula, submucous cleft palate, soft cleft palate, to complete cleft palate - OMIM, PMID:36901693 - Ankyloglossia/ bifid uvula/cleft palate reported in heterozygous females - Overall mild phenotype although PMID: 21375406 describes 1x TBX22 hemizygous individual with unilateral complete cleft lip and palate, ankyloglossia, hypodontia of the left maxillary second premolar, carpal bone anomalies, and hypoplastic thumb of the right hand. No other genes were tested. 2. Abruzzo-Erickson syndrome, MIM# 302905 PMID:22784330 - Single family reported with Abruzzo-Erickson syndrome, a syndromic form of cleft palate. Did not find additional reports on this phenotype; to: 1. Cleft palate with ankyloglossia (MIM# 303400) - More than 10 families reported with cleft palate/ankyloglossia and variants in this gene. - PMID:36901693 - Characterised by a cleft palate phenotype that is most often present in males and ranges from a high-arched palate, bifid uvula, submucous cleft palate, soft cleft palate, to complete cleft palate - OMIM, PMID:36901693 - Ankyloglossia/ bifid uvula/cleft palate reported in heterozygous females - Overall mild phenotype although PMID: 21375406 describes 1x TBX22 hemizygous individual with unilateral complete cleft lip and palate, ankyloglossia, hypodontia of the left maxillary second premolar, carpal bone anomalies, and hypoplastic thumb of the right hand. No other genes were tested. 2. Abruzzo-Erickson syndrome, MIM# 302905 PMID:22784330 - Single family reported with Abruzzo-Erickson syndrome, a syndromic form of cleft palate. Did not find additional reports on this phenotype |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | FANCE | Michelle Torres reviewed gene: FANCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 11001585, 31586946, 7662964, 9382107, 9147877, 10205272; Phenotypes: Fanconi anemia, complementation group E MIM#600901; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | CFI | Michelle Torres reviewed gene: CFI: Rating: GREEN; Mode of pathogenicity: None; Publications: 28942469; Phenotypes: Complement factor I deficiency MIM#610984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | NDUFS6 | Ee Ming Wong reviewed gene: NDUFS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15372108, 19259137, 30948790; Phenotypes: Mitochondrial complex I deficiency, nuclear type 9 (MIM#618232); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | SDHAF1 | Crystle Lee reviewed gene: SDHAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19465911, 22995659; Phenotypes: Mitochondrial complex II deficiency, nuclear type 2, MIM#619166; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.992 | MTR | Ee Ming Wong reviewed gene: MTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8968736, 8968737, 9683607, 12068375; Phenotypes: Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.978 | NDUFS2 | Kate Scarff reviewed gene: NDUFS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31411514, 22036843, 20819849, 11220739, 23266820, 31411514; Phenotypes: Mitochondrial complex I deficiency, nuclear type 6, MIM #618228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.921 | OCLN | Zornitza Stark Phenotypes for gene: OCLN were changed from Band-like calcification with simplified gyration and polymicrogyria, 251290 (3) to Pseudo-TORCH syndrome 1, MIM#251290 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.917 | COX10 | Zornitza Stark Phenotypes for gene: COX10 were changed from Leigh syndrome due to mitochondrial COX4 deficiency, 256000 (3) to Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.900 | FOXRED1 | Zornitza Stark Phenotypes for gene: FOXRED1 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 19, MIM# 618241 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.862 | CFD | Zornitza Stark Phenotypes for gene: CFD were changed from Complement factor D deficiency, 613912 (3) to Complement factor D deficiency, MIM# 613912 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.860 | CFD | Zornitza Stark reviewed gene: CFD: Rating: GREEN; Mode of pathogenicity: None; Publications: 11457876, 16527897, 31440263; Phenotypes: Complement factor D deficiency, MIM# 613912; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.836 | FOXRED1 | Lauren Thomas reviewed gene: FOXRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33613441, 20858599; Phenotypes: Mitochondrial complex I deficiency, nuclear type 19, MIM# 618241; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.836 | COX10 | Lauren Thomas reviewed gene: COX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 10767350, 12928484, 15455402, 27290639; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 3, MIM# 619046; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.817 | MED25 | Zornitza Stark Phenotypes for gene: MED25 were changed from Basel-Vanagait-Smirin-Yosef syndrome, 616449 (3) to Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449; congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome MONDO:0014643 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.804 | LYRM7 | Zornitza Stark Phenotypes for gene: LYRM7 were changed from Mitochondrial complex III deficiency, nuclear type 8, 615838 (3), Autosomal recessive to Mitochondrial complex III deficiency, nuclear type 8, MIM#615838, Autosomal recessive | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.798 | LRPPRC | Zornitza Stark Phenotypes for gene: LRPPRC were changed from Leigh syndrome, French-Canadian type, 220111 (3) to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.788 | TMEM70 | Zornitza Stark Phenotypes for gene: TMEM70 were changed from Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052 (3) to Mitochondrial disease MONDO:0044970 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.740 | SCO2 | Zornitza Stark Phenotypes for gene: SCO2 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377 (3) to Mitochondrial complex IV deficiency, nuclear type 2 MIM#604377 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.722 | MED25 | Marta Cifuentes Ochoa reviewed gene: MED25: Rating: GREEN; Mode of pathogenicity: None; Publications: 25792360, 32816121, 25527630, 30800049, 32324310, 19290556; Phenotypes: Basel-Vanagait-Smirin-Yosef syndrome, MIM# 616449, congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome MONDO:0014643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.714 | LYRM7 | Cassandra Muller reviewed gene: LYRM7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26912632, 24014394; Phenotypes: Mitochondrial complex III deficiency, nuclear type 8, 615838 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.708 | LRPPRC | Cassandra Muller reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 12529507, 12529507, 26510951, 21266382; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) 220111 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.683 | NDUFAF2 | Zornitza Stark Phenotypes for gene: NDUFAF2 were changed from Leigh syndrome, 256000 (3) to Mitochondrial complex I deficiency, nuclear type 10, MIM#618233 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.650 | NDUFAF6 | Zornitza Stark Phenotypes for gene: NDUFAF6 were changed from Leigh syndrome due to mitochondrial complex I deficiency, 256000 (3) to Leigh syndrome MONDO:0009723; Mitochondrial complex I deficiency, nuclear type 17 MIM#618239 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.633 | SCO2 | Andrew Coventry reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15210538, 18924171, 22231385, 10545952, 10749987; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 2 MIM#604377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.633 | IMPG2 |
Andrew Coventry changed review comment from: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152). - biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy. PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified. - Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype. Further studies and evidence: Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice) Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones. ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants curated were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796). RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2.; to: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152). - biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy. PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified. - Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype. Age of onset: PMID 34990796 - 16yo had night blindness and photophobia. Had 22y.o. sibling that was severely affected. Age of initial onset of visual symptoms said to be ~2-4 years of age. PMID 31264916 - 8y.o. with photophobia and myopia, 4y.o. with light sensitivity. 17yo with poor vision 'since childhood', 17yo with poor vision since birth and poor night vision, 45yo with poor night vision - starting at 6yo and progressing loss of central vision. PMID 24876279 - age of onset of patients studied: 1, 5, 6, 1, 2, 3, 2, 3, 1, 4, 1, 2, 1, 2, 6, 1, 1. Symptoms variable, including night blindness, decrease of visual acuity, loss of visual field. Further studies and evidence: Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice) Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones. ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants curated were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796). RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.633 | NDUFAF2 | Crystle Lee reviewed gene: NDUFAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38419071; Phenotypes: Mitochondrial complex I deficiency, nuclear type 10, MIM#618233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.633 | NDUFAF6 | Andrew Coventry reviewed gene: NDUFAF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30642748, 18614015, 30642748, 29531337, 27623250, 28639102, 31967322, 32020600, 22019594, 25613900, 26741492, 35664867; Phenotypes: Leigh syndrome MONDO:0009723, Mitochondrial complex I deficiency, nuclear type 17 MIM#618239; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.546 | IMPG2 |
Andrew Coventry changed review comment from: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152). - biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy. PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified. - Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype. Further studies and evidence: Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice) Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones. ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796). RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2.; to: Retinitis pigmentosa 56 - is an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. Features include night blindness, progressive visual loss, macular retinal pigment epithelium (RPE) mottling / atrophy, decreased ERG amplitudes (affecting rods more severely than cones), colour vision defect, peripheral visual field loss, central scotoma, retinal blood vessel attenuation, and/or optic disc pallor. These features are largely distinct from the vitelliform macular dystrophy phenotype (MIM#616152). - biallelic loss-of-function consistently associates with retinitis pigmentosa, while monoallelic loss-of-function consistently associates with vitelliform macular dystrophy. PMID: 20673862 - 2 families each with 3 affected sibs. Additional 10 index cases identified. - Those with nonsenses showed early-onset RP, patient with missense variants had a milder maculopathy phenotype. Further studies and evidence: Mouse models present exhibiting RP phenotype. (PMID: 38217426 - indicates missense variants had minimal retinal pathology in mice) Functional study present using patient derived iPS (PMID: 36206764) - confirmed LoF due to lack of expression or lack os post-translational modifications - destabilising outer segments of rods and cones. ClinGen - curation definitive for AR RP phenotype in association with gene IMPG2, with 10 suspected disease-causing variants scored as part of their curation (five nonsense, one frameshift, one canonical splice site disruption, one in-frame exon deletion, and two missense). Variants curated were in 8 probands (PMID: 24876279, PMID: 20673862, PMID: 31264916, PMID: 34990796). RP genes already screened for by 1000+, consider above adequate evidence to upgrade to green status for inclusion in v2. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.546 | IFNGR1 |
Andrew Coventry changed review comment from: Multiple families with recessive disease reported, reviewed in PMID 15589309. Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. The disorder can thus be categorized as a form of mendelian susceptibility to mycobacterial disease (MSMD). Bacillus Calmette-Guerin (BCG) and environmental mycobacteria are the most frequent pathogens, and infection typically begins before the age of 3 years. Recessive deficiency is thought to result in complete loss of cellular response to IFNG and absence of surface IFNGR1 expression. Animal models present. Note: AD condition associated with this gene - Immunodeficiency 27B, mycobacteriosis, MIM#615978. Dominant deficiency is typically due to cytoplasmic domain truncations resulting in accumulation of non-functional IFNGR1 proteins that may impede the function of molecules encoded by the wildtype allele, thereby leading to diminished but not absent responsiveness to IFNG. Common deletions at and around nucleotide 818. (PMID: 10192386); to: Multiple families with recessive disease reported, reviewed in PMID 15589309. Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. The disorder can thus be categorized as a form of mendelian susceptibility to mycobacterial disease (MSMD). Bacillus Calmette-Guerin (BCG) and environmental mycobacteria are the most frequent pathogens, and infection typically begins before the age of 3 years. Recessive deficiency is thought to result in complete loss of cellular response to IFNG and absence of surface IFNGR1 expression. Animal models present. Note: AD condition associated with this gene - Immunodeficiency 27B, mycobacteriosis, MIM#615978. Dominant deficiency is typically due to cytoplasmic domain truncations resulting in accumulation of non-functional IFNGR1 proteins that may impede the function of molecules encoded by the wildtype allele, thereby leading to diminished but not absent responsiveness to IFNG. Deletions including nucleotide 818 reported. (PMID: 10192386) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.525 | SPG11 |
Lucy Spencer changed review comment from: OMIM: Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years. Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. ClinGen lumps all 3 conditions under spastic paraplegia 11 Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010).; to: OMIM: Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years. Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010). These 3 conditions represent a spectrum of disease and ClinGen lumps all 3 conditions under hereditary spastic paraplegia 11 MONDO:0011445 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.505 | FANCF | Zornitza Stark Phenotypes for gene: FANCF were changed from Fanconi anemia, complementation group F, 603467 (3) to Fanconi anaemia, complementation group F, MIM#603467 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.489 | COX15 | Zornitza Stark Phenotypes for gene: COX15 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119 (3) to Mitochondrial complex IV deficiency, nuclear type 6, MIM #615119 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.486 | COX15 | Kate Scarff reviewed gene: COX15: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15235026, 12474143, 32232962; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 6, MIM #615119; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.486 | FANCF | Andrew Coventry reviewed gene: FANCF: Rating: GREEN; Mode of pathogenicity: None; Publications: 10615118 31288759 20301575; Phenotypes: Fanconi anemia, complementation group F MIM#603467; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.486 | SPG11 |
Lucy Spencer changed review comment from: OMIM: Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years. Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010).; to: OMIM: Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016). Mean age of onset 11.4 years. Hereditary spastic paraplegia (SPG or HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. SPG11 is a form of complicated SPG, in that it has neurologic features in addition to spasticity. ClinGen lumps all 3 conditions under spastic paraplegia 11 Autosomal recessive juvenile amyotrophic lateral sclerosis-5 (ALS5) is a neurodegenerative disorder characterized by onset of upper and lower motor neuron signs before age 25. Affected individuals have progressive spasticity of limb and facial muscles associated with distal amyotrophy. The disorder is slowly progressive, with cases of prolonged survival of more than 3 decades (summary by Orlacchio et al., 2010). |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.476 | KRT14 | Zornitza Stark Phenotypes for gene: KRT14 were changed from Epidermolysis bullosa simplex, recessive 1, 601001 (3) to Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive MIM# 601001; MONDO:0010976 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.470 | KRT14 | Marta Cifuentes Ochoa reviewed gene: KRT14: Rating: GREEN; Mode of pathogenicity: None; Publications: 29024068; Phenotypes: Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive MIM# 601001, MONDO:0010976; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.420 | FANCI | Lisa Norbart reviewed gene: FANCI: Rating: GREEN; Mode of pathogenicity: None; Publications: 17452773, 20301575, 26590883; Phenotypes: Fanconi anemia, complementation group I, MIM#609053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.420 | FANCG | Lisa Norbart reviewed gene: FANCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 9806548, 12552564; Phenotypes: Fanconi anemia, complementation group G, MIM#614082; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.418 | NDUFAF5 | Zornitza Stark Phenotypes for gene: NDUFAF5 were changed from Mitochondrial complex 1 deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 16 MIM#618238 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.417 | NDUFA1 | Zornitza Stark Phenotypes for gene: NDUFA1 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.408 | BCS1L | Zornitza Stark Phenotypes for gene: BCS1L were changed from GRACILE syndrome, 603358 (3) to GRACILE syndrome, MIM#603358; Mitochondrial complex III deficiency, nuclear type 1, MIM#124000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.390 | NDUFAF5 | Lucy Spencer reviewed gene: NDUFAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 16 MIM#618238; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.390 | NDUFA1 | Lucy Spencer reviewed gene: NDUFA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.390 | BCS1L | Lisa Norbart reviewed gene: BCS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 26563427, 17314340; Phenotypes: GRACILE syndrome, MIM#603358, Mitochondrial complex III deficiency, nuclear type 1, MIM#124000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.382 | NDUFS8 | Lilian Downie Phenotypes for gene: NDUFS8 were changed from Leigh syndrome due to mitochondrial complex I deficiency, 256000 (3) to Mitochondrial complex I deficiency, nuclear type 2 (MIM#618222) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.359 | NDUFS8 | Lauren Rogers reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 23430795, 36101822; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 (MIM#618222); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.336 | RFXAP | Lilian Downie Phenotypes for gene: RFXAP were changed from Bare lymphocyte syndrome, type II, complementation group D, 209920 (3) to MHC class II deficiency 4 MIM#620817 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.287 | NYX | Andrew Coventry reviewed gene: NYX: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062471 11062472 16670814 23714322 34064005 34165036 12506099 11062471 17004930; Phenotypes: Night blindness, congenital stationary (complete), 1A, X-linked MIM310500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.287 | MPLKIP | Andrew Coventry reviewed gene: MPLKIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 15645389 16977596; Phenotypes: Trichothiodystrophy 4, nonphotosensitive MIM#234050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.262 | CFH | Cassandra Muller reviewed gene: CFH: Rating: AMBER; Mode of pathogenicity: None; Publications: 7742208, 9312129, 10803850, 14978182; Phenotypes: Complement factor H deficiency, 609814 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.248 | GNE |
Andrew Coventry changed review comment from: Nonaka myopathy - Well established gene disease relationship. However, age of onset of myopathy reported to usually occur between age 20 and 40. Marginal for childhood onset condition. Thrombocytopenia - well reported association of affected individuals experiencing bleeding episodes that commence from neonatal to early childhood. Myopathy variably reported in those affected - possibly due to young age of individuals presenting with bleeding symptoms. Myopathy, when reported, occurs at similar age of onset to Nonaka. Publication (25257349) indicates myopathy onset in affected sibs at mid-late teens. Also reported renal complications at age 7. Mouse model for GNE knockout shows renal involvement (PMID: 17549255). Condition reported to have caused cerebral haemorrhages in neonatal period (PMID:29941673). Unsure if phenotypic variability of condition, and isolated bleeding phenotype (as in ClinGen) suitable or adequate for screening context.; to: Nonaka myopathy - Well established gene disease relationship. However, age of onset of myopathy reported to usually occur between age 20 and 40. Myopathy then progresses, usually over ~10 year period to then require wheelchair assistance for mobility. Severe condition but onset is marginal for childhood onset screening context. Thrombocytopenia - well reported association of affected individuals experiencing bleeding episodes that commence from neonatal to early childhood. Myopathy variably reported in those affected - possibly due to young age of individuals presenting with bleeding symptoms. Myopathy, when reported, occurs at similar age of onset to Nonaka. Publication (25257349) indicates myopathy onset in affected sibs at mid-late teens. Also reported renal complications at age 7. Mouse model for GNE knockout shows renal involvement (PMID: 17549255). Condition reported to have caused cerebral haemorrhages in neonatal period (PMID:29941673). Unsure if phenotypic variability of condition, and isolated bleeding phenotype (as in ClinGen) suitable or adequate for screening context. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.248 | FANCC | Shakira Heerah reviewed gene: FANCC: Rating: GREEN; Mode of pathogenicity: None; Publications: 29376519, 31044565, 30792206, 28717661; Phenotypes: Fanconi anemia, complementation group C, 227645 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.234 | SURF1 | Zornitza Stark Added comment: Comment when marking as ready: Agree Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110 is the appropriate term to use. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.234 | SURF1 | Zornitza Stark Phenotypes for gene: SURF1 were changed from Leigh syndrome, due to COX deficiency, 256000 (3) to Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.206 | APOPT1 | Zornitza Stark Phenotypes for gene: APOPT1 were changed from Mitochondrial complex IV deficiency, 220110 (3) to Mitochondrial complex IV deficiency, MIM#220110 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.168 | FANCB | Lucy Spencer reviewed gene: FANCB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group B, MIM#300514; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.147 | SURF1 | Lilian Downie Added comment: Comment when marking as ready: Consider most appropriate name- literature commonly refers to as Leigh syndrome but MIM 256000 doesn't have SURF1 attached to it. No overarching MONDO. Maybe MItochondrial complex IV deficiency MIM220110 is the most appropriate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.143 | CSMD1 |
Krithika Murali gene: CSMD1 was added gene: CSMD1 was added to Prepair 1000+. Sources: Literature Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CSMD1 were set to PMID:38816421 Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038 Review for gene: CSMD1 was set to GREEN Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected. Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.142 | APOPT1 | Cassandra Muller reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25175347, 32637636; Phenotypes: Mitochondrial complex IV deficiency, 220110 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.133 | COX20 | Lilian Downie Phenotypes for gene: COX20 were changed from Mitochondrial complex IV deficiency, 220110 (3) to Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.76 | CYP11A1 | Andrew Coventry reviewed gene: CYP11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12161514 16705068 18182448 28425981; Phenotypes: Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete MIM#613743; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.76 | COX20 | Lucy Spencer reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: None; Publications: 33751098; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, MIM#619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.65 | SURF1 | Lauren Rogers reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23829769; Phenotypes: Charcot-Marie-Tooth disease, type 4K MIM#616684, Mitochondrial complex IV deficiency, nuclear type 1 MIM#220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.65 | CD55 | Lucy Spencer reviewed gene: CD55: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28657829; Phenotypes: Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.21 | GFM1 |
Lauren Rogers changed review comment from: Well established gene-disease association. Onset at birth with death within first months of life No treatment available Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V ; to: Well established gene-disease association. Onset at birth with death within first months of life No treatment available |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.16 | GFM1 |
Lauren Rogers changed review comment from: Well established gene-disease association. Onset at birth with death within first months of life No treatment available Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V Detection on NBS would establish diagnosis early and allow palliative treatment; to: Well established gene-disease association. Onset at birth with death within first months of life No treatment available Non-genetic confirmatory test: - Fibroblasts show decreased activity of mitochondrial respiratory complex I, complex III, complex IV, and complex V |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.7 | ACAD9 | Karina Sandoval reviewed gene: ACAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:30025539, 26475292; Phenotypes: Mitochondrial complex I deficiency, nuclear type 20 (MIM#611126); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | UBE2T | Seb Lunke Added phenotypes Fanconi anemia, complementation group T, 616435 (3) for gene: UBE2T | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | PET100 | Seb Lunke Added phenotypes Mitochondrial complex IV deficiency, 220110 (3) for gene: PET100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | NDUFV1 | Seb Lunke Added phenotypes Mitochondrial complex I deficiency, 252010 (3) for gene: NDUFV1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | NDUFS6 | Seb Lunke Added phenotypes Mitochondrial complex I deficiency, 252010 (3) for gene: NDUFS6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | NDUFAF5 | Seb Lunke Added phenotypes Mitochondrial complex 1 deficiency, 252010 (3) for gene: NDUFAF5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | MTR | Seb Lunke Added phenotypes Homocystinuria-megaloblastic anemia, cblG complementation type, 250940 (3) for gene: MTR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | MPL | Seb Lunke Added phenotypes Thrombocytopenia, congenital amegakaryocytic, 604498 (3) for gene: MPL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | MMAB | Seb Lunke Added phenotypes Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type, 251110 (3) for gene: MMAB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | KRT14 | Seb Lunke Added phenotypes Epidermolysis bullosa simplex, recessive 1, 601001 (3) for gene: KRT14 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FOXRED1 | Seb Lunke Added phenotypes Mitochondrial complex I deficiency, 252010 (3) for gene: FOXRED1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCL | Seb Lunke Added phenotypes Fanconi anemia, complementation group L, 614083 (3) for gene: FANCL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCI | Seb Lunke Added phenotypes Fanconi anemia, complementation group I, 609053 (3) for gene: FANCI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCG | Seb Lunke Added phenotypes Fanconi anemia, complementation group G, 614082 (3) for gene: FANCG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCF | Seb Lunke Added phenotypes Fanconi anemia, complementation group F, 603467 (3) for gene: FANCF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCE | Seb Lunke Added phenotypes Fanconi anemia, complementation group E, 600901 (3) for gene: FANCE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCD2 | Seb Lunke Added phenotypes Fanconi anemia, complementation group D2, 227646 (3) for gene: FANCD2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCC | Seb Lunke Added phenotypes Fanconi anemia, complementation group C, 227645 (3) for gene: FANCC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCB | Seb Lunke Added phenotypes Fanconi anemia, complementation group B, 300514 (3) for gene: FANCB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | FANCA | Seb Lunke Added phenotypes Fanconi anemia, complementation group A, 227650 (3) for gene: FANCA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | ERCC4 | Seb Lunke Added phenotypes Fanconi anemia, complementation group Q, 615272 (3) for gene: ERCC4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | CYP11A1 | Seb Lunke Added phenotypes Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, 613743 (3) for gene: CYP11A1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | CIITA | Seb Lunke Added phenotypes Bare lymphocyte syndrome, type II, complementation group A, 209920 (3) for gene: CIITA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | ACAD9 | Seb Lunke Added phenotypes Mitochondrial complex I deficiency due to ACAD9 deficiency, 611126 (3) for gene: ACAD9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.0 | BRIP1 |
Himanshu Goel gene: BRIP1 was added gene: BRIP1 was added to Prepair 1000+. Sources: Literature Mode of inheritance for gene: BRIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BRIP1 were set to 16116423 Phenotypes for gene: BRIP1 were set to Fanconi Anaemia Penetrance for gene: BRIP1 were set to Complete Mode of pathogenicity for gene: BRIP1 was set to Other Review for gene: BRIP1 was set to GREEN gene: BRIP1 was marked as current diagnostic Added comment: Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.119 | PCDH19 |
Crystle Lee gene: PCDH19 was added gene: PCDH19 was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: PCDH19 was set to Other Publications for gene: PCDH19 were set to 18469813; 30287595 Phenotypes for gene: PCDH19 were set to Developmental and epileptic encephalopathy 9 (MIM#300088) Review for gene: PCDH19 was set to AMBER Added comment: XLD. Affects heterozygous females, hemizygous males are mainly unaffected > 3 unrelated families with phenotype, > 3 de novo mutation carriers with phenotype Evidence of mosaicism and incomplete penetrance Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | WNT10A |
Crystle Lee gene: WNT10A was added gene: WNT10A was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: WNT10A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: WNT10A were set to 19559398; 30426266 Phenotypes for gene: WNT10A were set to Odontoonychodermal dysplasia 257980 AR; Schopf-Schulz-Passarge syndrome 224750 AR; Tooth agenesis, selective, 4 150400 AR, AD Penetrance for gene: WNT10A were set to Incomplete Review for gene: WNT10A was set to RED Added comment: Well established gene disease association. Genotype-phenotype correlation is unclear. The same variant has been associated with all 3 phenotypes and both AR and AD inheritance. Variable expressivity, however milder phenotypes seem to be associated with AD (PMID: 19559398; 30426266) Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | TECPR2 |
Crystle Lee gene: TECPR2 was added gene: TECPR2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TECPR2 were set to 23176824; 26542466; 35130874 Phenotypes for gene: TECPR2 were set to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, MIM#615031 Review for gene: TECPR2 was set to GREEN Added comment: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | PYGM |
Crystle Lee gene: PYGM was added gene: PYGM was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PYGM were set to McArdle disease (MIM#232600) Review for gene: PYGM was set to AMBER Added comment: Gene-disease association for bi-allelic variants is well established. McCardle disease: glycogen storage disease type V (GSD5), characterized by onset of exercise intolerance and muscle cramps in childhood or adolescence. Transient myoglobinuria may occur after exercise, due to rhabdomyolysis. Severe myoglobinuria may lead to acute renal failure. Patients may report muscle weakness, myalgia, and lack of endurance since childhood or adolescence. Later in adult life, there is persistent and progressive muscle weakness and atrophy with fatty replacement. McArdle disease is a relatively benign disorder, except for possible renal failure as a complication of myoglobinuria Clinical heterogeneity exists; about 10% of all affected individuals have mild manifestations (e.g., fatigue or poor stamina without contractures) and remain virtually asymptomatic during daily activities of living(Gene Reviews) Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | MEFV |
Crystle Lee gene: MEFV was added gene: MEFV was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: MEFV was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Phenotypes for gene: MEFV were set to Familial Mediterranean fever, AR (MIM#249100) Penetrance for gene: MEFV were set to Incomplete Review for gene: MEFV was set to AMBER Added comment: Well established association. Predominantly bi-allelic, though a limited range of heterozygous variants have been associated with disease. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.61 | HFE |
Crystle Lee gene: HFE was added gene: HFE was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: HFE was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HFE were set to Hemochromatosis (MIM#235200) Penetrance for gene: HFE were set to Incomplete Review for gene: HFE was set to RED Added comment: Well established gene disease association. HFE hemochromatosis is an adult-onset, treatable disorder with low clinical penetrance (Gene Reviews). Not suitable for population carrier screening. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.61 | GP9 |
Crystle Lee gene: GP9 was added gene: GP9 was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: GP9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GP9 were set to 8049428; 33553065; 32030720; 31484196 Phenotypes for gene: GP9 were set to Bernard-Soulier syndrome, type C (MIM#231200) Review for gene: GP9 was set to AMBER Added comment: Bernard-Soulier syndrome is a bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5. At least 3 unrelated families reported, animal model. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.61 | GJB1 |
Crystle Lee gene: GJB1 was added gene: GJB1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: GJB1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: GJB1 were set to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 (MIM#302800) Review for gene: GJB1 was set to AMBER Added comment: CMTX has both demyelinating and axonal features. Well established gene-disease association, over 100 families reported. Variable phenotype with incomplete penetrance (OMIM) PMID 31842800: Three unrelated males with GJB1 variants and recurrent episodes of reversible posterior leukoencephalopathy reported. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.31 | UQCRQ | Crystle Lee reviewed gene: UQCRQ: Rating: RED; Mode of pathogenicity: None; Publications: 18439546; Phenotypes: Mitochondrial complex III deficiency, nuclear type 4 (MIM#615159); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.19 | NDUFA11 | Zornitza Stark Phenotypes for gene: NDUFA11 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFA11 | Crystle Lee reviewed gene: NDUFA11: Rating: RED; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | UQCRC2 |
Zornitza Stark gene: UQCRC2 was added gene: UQCRC2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red Mode of inheritance for gene: UQCRC2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UQCRC2 were set to Mitochondrial complex III deficiency, nuclear type 5, 615160 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | UQCRQ |
Zornitza Stark gene: UQCRQ was added gene: UQCRQ was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: UQCRQ was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UQCRQ were set to Mitochondrial complex III deficiency, nuclear type 4, 615159 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | UBE2T |
Zornitza Stark gene: UBE2T was added gene: UBE2T was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UBE2T were set to Fanconi anemia, complementation group T, 616435 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | TTC19 |
Zornitza Stark gene: TTC19 was added gene: TTC19 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: TTC19 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TTC19 were set to Mitochondrial complex III deficiency, nuclear type 2, 615157 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | TMEM70 |
Zornitza Stark gene: TMEM70 was added gene: TMEM70 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: TMEM70 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TMEM70 were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | SDHAF1 |
Zornitza Stark gene: SDHAF1 was added gene: SDHAF1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: SDHAF1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SDHAF1 were set to Mitochondrial complex II deficiency, 252011 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | RFXAP |
Zornitza Stark gene: RFXAP was added gene: RFXAP was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: RFXAP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RFXAP were set to Bare lymphocyte syndrome, type II, complementation group D, 209920 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | RFXANK |
Zornitza Stark gene: RFXANK was added gene: RFXANK was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: RFXANK was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RFXANK were set to MHC class II deficiency, complementation group B, 209920 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | PLEC |
Zornitza Stark gene: PLEC was added gene: PLEC was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: PLEC was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PLEC were set to Epidermolysis bullosa simplex with pyloric atresia, 612138 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | PET100 |
Zornitza Stark gene: PET100 was added gene: PET100 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: PET100 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PET100 were set to Mitochondrial complex IV deficiency, 220110 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | OCLN |
Zornitza Stark gene: OCLN was added gene: OCLN was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: OCLN was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: OCLN were set to Band-like calcification with simplified gyration and polymicrogyria, 251290 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NYX |
Zornitza Stark gene: NYX was added gene: NYX was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NYX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: NYX were set to Night blindness, congenital stationary (complete), 1A, X-linked, MIM #310500 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NUBPL |
Zornitza Stark gene: NUBPL was added gene: NUBPL was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NUBPL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NUBPL were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFV2 |
Zornitza Stark gene: NDUFV2 was added gene: NDUFV2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFV2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFV2 were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFV1 |
Zornitza Stark gene: NDUFV1 was added gene: NDUFV1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFV1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFV1 were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFS8 |
Zornitza Stark gene: NDUFS8 was added gene: NDUFS8 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFS8 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFS8 were set to Leigh syndrome due to mitochondrial complex I deficiency, 256000 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFS6 |
Zornitza Stark gene: NDUFS6 was added gene: NDUFS6 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFS6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFS6 were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFS2 |
Zornitza Stark gene: NDUFS2 was added gene: NDUFS2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFS2 were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFS1 |
Zornitza Stark gene: NDUFS1 was added gene: NDUFS1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFS1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFS1 were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFAF6 |
Zornitza Stark gene: NDUFAF6 was added gene: NDUFAF6 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFAF6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFAF6 were set to Leigh syndrome due to mitochondrial complex I deficiency, 256000 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFAF5 |
Zornitza Stark gene: NDUFAF5 was added gene: NDUFAF5 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFAF5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFAF5 were set to Mitochondrial complex 1 deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFA11 |
Zornitza Stark gene: NDUFA11 was added gene: NDUFA11 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFA11 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NDUFA11 were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | NDUFA1 |
Zornitza Stark gene: NDUFA1 was added gene: NDUFA1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: NDUFA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: NDUFA1 were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | MTR |
Zornitza Stark gene: MTR was added gene: MTR was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: MTR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MTR were set to Homocystinuria-megaloblastic anemia, cblG complementation type, 250940 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | MPLKIP |
Zornitza Stark gene: MPLKIP was added gene: MPLKIP was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: MPLKIP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MPLKIP were set to Trichothiodystrophy 4, nonphotosensitive, 234050 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | MPL |
Zornitza Stark gene: MPL was added gene: MPL was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: MPL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MPL were set to Thrombocytopenia, congenital amegakaryocytic, 604498 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | MMAB |
Zornitza Stark gene: MMAB was added gene: MMAB was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: MMAB was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MMAB were set to Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type, 251110 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | LYRM7 |
Zornitza Stark gene: LYRM7 was added gene: LYRM7 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: LYRM7 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LYRM7 were set to Mitochondrial complex III deficiency, nuclear type 8, 615838 (3), Autosomal recessive |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | KRT5 |
Zornitza Stark gene: KRT5 was added gene: KRT5 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: KRT5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: KRT5 were set to Epidermolysis bullosa simplex, recessive 1, 601001 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | KRT14 |
Zornitza Stark gene: KRT14 was added gene: KRT14 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: KRT14 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: KRT14 were set to Epidermolysis bullosa simplex, recessive 1, 601001 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | GPR179 |
Zornitza Stark gene: GPR179 was added gene: GPR179 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: GPR179 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GPR179 were set to Night blindness, congenital stationary (complete), 1E, autosomal recessive, 614565 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FOXRED1 |
Zornitza Stark gene: FOXRED1 was added gene: FOXRED1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FOXRED1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FOXRED1 were set to Mitochondrial complex I deficiency, 252010 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCL |
Zornitza Stark gene: FANCL was added gene: FANCL was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FANCL were set to Fanconi anemia, complementation group L, 614083 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCI |
Zornitza Stark gene: FANCI was added gene: FANCI was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCI was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FANCI were set to Fanconi anemia, complementation group I, 609053 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCG |
Zornitza Stark gene: FANCG was added gene: FANCG was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCG was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FANCG were set to Fanconi anemia, complementation group G, 614082 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCF |
Zornitza Stark gene: FANCF was added gene: FANCF was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCF was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FANCF were set to Fanconi anemia, complementation group F, 603467 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCE |
Zornitza Stark gene: FANCE was added gene: FANCE was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCE was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FANCE were set to Fanconi anemia, complementation group E, 600901 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCD2 |
Zornitza Stark gene: FANCD2 was added gene: FANCD2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCD2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FANCD2 were set to Fanconi anemia, complementation group D2, 227646 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCC |
Zornitza Stark gene: FANCC was added gene: FANCC was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCC was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FANCC were set to Fanconi anemia, complementation group C, 227645 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCB |
Zornitza Stark gene: FANCB was added gene: FANCB was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCB was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FANCB were set to Fanconi anemia, complementation group B, 300514 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | FANCA |
Zornitza Stark gene: FANCA was added gene: FANCA was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FANCA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FANCA were set to Fanconi anemia, complementation group A, 227650 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | ERCC4 |
Zornitza Stark gene: ERCC4 was added gene: ERCC4 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ERCC4 were set to Fanconi anemia, complementation group Q, 615272 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | CYP11A1 |
Zornitza Stark gene: CYP11A1 was added gene: CYP11A1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: CYP11A1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CYP11A1 were set to Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, 613743 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | COX20 |
Zornitza Stark gene: COX20 was added gene: COX20 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: COX20 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: COX20 were set to Mitochondrial complex IV deficiency, 220110 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | CIITA |
Zornitza Stark gene: CIITA was added gene: CIITA was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: CIITA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CIITA were set to Bare lymphocyte syndrome, type II, complementation group A, 209920 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | CFI |
Zornitza Stark gene: CFI was added gene: CFI was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: CFI was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CFI were set to Complement factor I deficiency, 610984 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | CFH |
Zornitza Stark gene: CFH was added gene: CFH was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: CFH was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CFH were set to Complement factor H deficiency, 609814 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | CFD |
Zornitza Stark gene: CFD was added gene: CFD was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: CFD was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CFD were set to Complement factor D deficiency, 613912 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | CD55 |
Zornitza Stark gene: CD55 was added gene: CD55 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: CD55 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CD55 were set to Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, 226300 (3), Autosomal recessive |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | APOPT1 |
Zornitza Stark gene: APOPT1 was added gene: APOPT1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: APOPT1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: APOPT1 were set to Mitochondrial complex IV deficiency, 220110 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | ACAD9 |
Zornitza Stark gene: ACAD9 was added gene: ACAD9 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: ACAD9 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ACAD9 were set to Mitochondrial complex I deficiency due to ACAD9 deficiency, 611126 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||