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| Prepair 1000+ v1.1568 | DLAT |
Andrew Coventry gene: DLAT was added gene: DLAT was added to Prepair 1000+. Sources: Literature Mode of inheritance for gene: DLAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DLAT were set to 34138529; 16049940; 20022530; 29093066 Phenotypes for gene: DLAT were set to Leigh syndrome MONDO:0009723; Pyruvate dehydrogenase E2 deficiency MIM#245348 Review for gene: DLAT was set to GREEN Added comment: Clinical presentation is in infancy. Pyruvate dehydrogenase E2 deficiency is a mitochondrial disorder, mostly affects the brain and leads to decreased ATP production and energy deficit. Can manifest as a syndrome of neurologic signs (congenital microcephaly, hypotonia, epilepsy, and/or ataxia), brain impacts (dysgenesis of the corpus callosum, Leigh syndrome) and metabolic abnormalities (increased plasma pyruvate, lactic acidemia, and/or metabolic acidosis). Biochemical function, expression data, and model systems available. 1-4% of total PDE2D cases are due to variants in DLAT - associated with phenotype w/survival into childhood/adulthood, milder than other genes involved with condition. PMID: 16049940 - 2 unrelated patients with Episodic dystonia. Hypotonia and ataxia, being less prominent. Neuroradiological evidence of discrete lesions restricted to the globus pallidus, Male patient 1 - dystonic movements of the facial muscles and of his hands and feet.Developmental delay (12 words at age 4). Treatment has improved condition. Male patient 2 - presented at 11 months of age with episodic dystonia (up to 3hrs duration). 8 years of age, developmental delay, cannot walk. PMID: 29093066 - 2 siblings (both homozygous for c.470T>G; p.Val157Gly). Male sibling reported with intellectual disability and exercise-induced gait abnormalities. IQ of 44 at 8 years of age. Female sibling noted to have global delays with intellectual disability. PMID: 20022530 - two sisters with early onset episodic dystonia and pyruvate dehydrogenase deficiency. At least 6 cases, in 4 unrelated families as described in publications above. While reportedly milder than other presentations, appears severe presentation in absence of treatment. Other genes currently included: PDHA1, PDHB, PDP1. Sources: Literature |
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| Prepair 1000+ v1.1566 | SCNN1A |
Lauren Thomas changed review comment from: Well established gene-disease association. Childhood onset, potentially lethal salt wasting condition characterised by excess loss of salt in the urine and high concentrations of sodium in sweat, stool, and saliva. Treatment for this condition involves aggressive salt replacement and control of hyperkalemia. HGNC approved symbol/name: SCNN1A Is the phenotype(s) severe and onset <18yo? Yes Treatments available: Yes, supplementary sodium, but not mineralocorticoids Known technical challenges? No Gene reported in 3 independent families: Yes; to: Well established gene-disease association. Childhood onset, potentially lethal salt wasting condition characterised by excess loss of salt in the urine and high concentrations of sodium in sweat, stool, and saliva. Treatment for this condition involves aggressive salt replacement and control of hyperkalemia. HGNC approved symbol/name: SCNN1A Is the phenotype(s) severe and onset <18yo? Yes Treatments available: Yes, supplementary sodium, but not mineralocorticoids Known technical challenges? No Gene reported in 3 independent families: Yes NOTE: Limited evidence for association between mono-allelic variants and disease (bronchiectasis with or without elevated sweat chloride 2, MIM# 613021; Liddle syndrome 3, MIM# 618126) |
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| 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 |
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| Prepair 1000+ v1.352 | GATM | Lilian Downie Marked gene: GATM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.352 | GATM | Lilian Downie Gene: gatm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.352 | GATM | Lilian Downie Publications for gene: GATM were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.322 | GATM | Marta Cifuentes Ochoa reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 11555793, 27604308; Phenotypes: Cerebral creatine deficiency syndrome 3 MIM#612718, AGAT deficiency MONDO:0012996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.122 | ARV1 | Lilian Downie Added comment: Comment when marking as ready: Developmental and epileptic encephalopathy-38 (DEE38) is an autosomal recessive neurologic and neurodegenerative disorder characterized by the onset of various type of seizures usually between about 4 and 7 months of age. Prior to the onset of seizures, most infants show severely impaired global development, hypotonia with poor head control, and visual inattention with roving eye movements and nystagmus. Seizures are usually refractory to treatment and associated with status epilepticus. Patients have little or no development with inability to walk or speak, spasticity or abnormal movements, and often cortical blindness. There is failure to thrive, and many require tube-feeding. Death in early childhood due to aspiration or intractable epilepsy may occur. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.67 | ATM | Lilian Downie Marked gene: ATM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.67 | ATM | Lilian Downie Added comment: Comment when marking as ready: NB for reporting carrier mother may need additional breast cancer surveillance | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.67 | ATM | Lilian Downie Gene: atm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.67 | ATM | Lilian Downie Publications for gene: ATM were set to 30137827 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.66 | ATM | Lilian Downie Publications for gene: ATM were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.65 | ATM | Lauren Rogers reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 30137827; Phenotypes: Ataxia-telangiectasia, MIM# 208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.43 | COQ4 |
Lauren Rogers changed review comment from: At least 9 unrelated families reported. Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.; to: At least 9 unrelated families reported. Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations. |
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| Prepair 1000+ v1.43 | ALOXE3 |
Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3 Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here. Discussed 25/07/24- this can be a very severe form of ichthyosis, should be green and remain on this panel Treatments available: No specific treatment available (from babyscreen); to: HGNC approved symbol/name: ALOXE3 Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here. Treatments available: No specific treatment available (from babyscreen) |
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| Prepair 1000+ v1.43 | ALOXE3 |
Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3 Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here. Treatments available: No specific treatment available (from babyscreen); to: HGNC approved symbol/name: ALOXE3 Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here. Discussed 25/07/24- this can be a very severe form of ichthyosis, should be green and remain on this panel Treatments available: No specific treatment available (from babyscreen) |
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| Prepair 1000+ v1.43 | ALOXE3 |
Lucy Spencer changed review comment from: HGNC approved symbol/name: ALOXE3 Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here. Treatments available: No specific treatment available (from babyscreen) Known technical challenges? Y; to: HGNC approved symbol/name: ALOXE3 Is the phenotype(s) severe and onset <18yo ? Yes early onset; babyscreen review notes its congenital onset. However this gene causes ichthyosis and OMIM says "Affected individuals have a relatively mild ichthyosis phenotype". Im not sure its severe enough to include here. Treatments available: No specific treatment available (from babyscreen) |
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| Prepair 1000+ v1.43 | COQ4 |
Lauren Rogers changed review comment from: At least 9 unrelated families reported. Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.; to: At least 9 unrelated families reported. Primary coenzyme Q10 deficiency-7 (COQ10D7) is an autosomal recessive disorder resulting from mitochondrial dysfunction. Most patients have onset of severe cardiac or neurologic symptoms soon after birth. IUGR reported. Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations. |
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| 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 |
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| 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 |
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| Prepair 1000+ v1.9 | ALG12 |
Kate Scarff changed review comment from: HGNC approved symbol/name: ALG12 Is the phenotype(s) severe and onset <18yo ? Yes Features include impaired psychomotor development, dysmorphic features, failure to thrive, male genital hypoplasia, coagulation abnormalities, and immune deficiency. More variable features include skeletal dysplasia, cardiac anomalies, ocular abnormalities, and sensorineural hearing loss. Some patients die in the early neonatal or infantile period, whereas others are mildly affected and live to adulthood; to: HGNC approved symbol/name: ALG12 Is the phenotype(s) severe and onset <18yo ? Yes Features include impaired psychomotor development, dysmorphic features, failure to thrive, male genital hypoplasia, coagulation abnormalities, and immune deficiency. More variable features include skeletal dysplasia, cardiac anomalies, ocular abnormalities, and sensorineural hearing loss. Some patients die in the early neonatal or infantile period, whereas others are mildly affected and live to adulthood. No specific treatment at present. |
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| Prepair 1000+ v1.9 | AGL | Marta Cifuentes Ochoa commented on gene: AGL: Current Treatment high-fat, high-protein and low-carbohydrate diet with cornstarch supplementation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | GATM | Seb Lunke Added phenotypes Cerebral creatine deficiency syndrome 3, 612718 (3) for gene: GATM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | ATM | Seb Lunke Added phenotypes Ataxia-telangiectasia, 208900 (3) for gene: ATM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.61 | BTD |
Crystle Lee gene: BTD was added gene: BTD was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BTD were set to 16435182; 20301497; 32440248 Phenotypes for gene: BTD were set to Biotinidase deficiency (MIM#253260) Review for gene: BTD was set to RED Added comment: Well-established gene disease association. Genotype/phenotype correlations in biotinidase deficiency are not well established, decisions regarding treatment should be based on the results of enzyme activity rather than molecular genetic testing. May be challenging to predict phenotypic outcome in a carrier screening context. Sources: Literature |
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| Prepair 1000+ v0.0 | GATM |
Zornitza Stark gene: GATM was added gene: GATM was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: GATM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GATM were set to Cerebral creatine deficiency syndrome 3, 612718 (3) |
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| Prepair 1000+ v0.0 | ATM |
Zornitza Stark gene: ATM was added gene: ATM was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ATM were set to Ataxia-telangiectasia, 208900 (3) |
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