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| Skeletal dysplasia v0.303 | MEG3 |
Zornitza Stark gene: MEG3 was added gene: MEG3 was added to Skeletal dysplasia. Sources: Expert list SV/CNV, non-coding gene tags were added to gene: MEG3. Mode of inheritance for gene: MEG3 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: MEG3 were set to 33010492; 33746039; 33067531; 38212313 Phenotypes for gene: MEG3 were set to Kagami-Ogata syndrome, MIM# 608149 Review for gene: MEG3 was set to GREEN Added comment: Small deletions of MAG3 reported in multiple patients as one of the mechanisms of disease. Bell-shaped thorax and multiple other skeletal anomalies are a feature. Sources: Expert list |
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| Skeletal dysplasia v0.275 | FUZ |
Chirag Patel gene: FUZ was added gene: FUZ was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: FUZ was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FUZ were set to PMID: 38702430, 29068549, 34719684 Phenotypes for gene: FUZ were set to Ciliopathy_MONDO_0005308; skeletal ciliopathy Review for gene: FUZ was set to GREEN gene: FUZ was marked as current diagnostic Added comment: FUZ is crucial for the transport of components to the primary cilium and potentially promotes protein complex assembly necessary for downstream cilium formation and function. Previous studies have shown complete knockout of Fuz in a mouse model leads to prenatal lethality, coronal craniosynostosis, micrognathia, facial malformations, eye, and heart defects. Suggested as a skeletal ciliopathy disorder gene. PMID: 38702430 1 individual (from family with 2 affecteds) with orofaciodigital syndrome like phenotype (dysmorphism, bilateral foot preaxial polysyndactyly, right foot postaxial polysyndactyly, broad thumbs, bilateral 5th finger clinodactyly narrow chest, partial AVSD). They found a homozygous missense variant in FUZ [p.(Glu201Lys)]. Parents were heterozygous carriers. A sibling died at 18mths and had complete AVSD, bilateral cleft lip and palate, right 5th finger clinodactyly, and medially deviated/broad great toes. 1 fetus with orofaciodigital syndrome like phenotype (right cleft lip, 4 limb polydactyly, bilateral duplicated hallux, and AVSD). They found compound heterozygous variants in FUZ [p.(Val209_Leu212del) and p.(Glu201Lys)]. PMID: 29068549 1 fetus with lethal short-rib polydactyly syndrome II-like phenotype and a homozygous variant (c.98_111+9del) in FUZ. 1 individual with asphyxiating thoracic dystrophy (ATD) with polydactyly and a (unclear if homozygous) missense variant [p.(Arg284Leu)] in FUZ. PMID: 34719684 Monozygotic twins with craniosynostosis (1 x metopic, 1 x metopic/coronal) and a homozygous missense variant in FUZ [p.(Arg284Pro)]. They cultured primary osteoblasts and mouse embryonic fibroblasts from Fuz mutant mice. Loss of Fuz resulted in increased osteoblastic mineralisation, suggesting that the FUZ protein normally acts as a negative regulator of osteogenesis. Sources: Literature |
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| Skeletal dysplasia v0.265 | KIAA0586 |
Elena Savva gene: KIAA0586 was added gene: KIAA0586 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0586 were set to PMID: 36538006; 26096313; 26166481 Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23 MIM#616490; Short-rib thoracic dysplasia 14 with polydactyly MIM#616546 Review for gene: KIAA0586 was set to GREEN Added comment: PMID: 36538006 - fetus with post-axial polydactyly, short limbs and persistent left superior vena cava (PLSVC) with a dilated coronary sinus. Chet variants c.3940+1G>A and c.3303G>A (synonymous) were identified. Functional studies support an impact for both variants. PMID: 26096313 - 9 unrelated families with Joubert syndrome. MRI shows the molar tooth sign in 3/3 scanned patients. Patients tended to have biallelic PTCs, though missense also reported. p.Arg143Lysfs*4 appears to be a recurring mutation, seen in patients either as a homozygote or in chet with another unique mutation in 7/9 families. Interestingly these 7 families were of different ethnicity PMID: 26166481 - Four unrelated families reported with a severe neurological/skeletal phenotype. However, note same variant identified in three of the families, indicative of founder effect. Gene is also associated with Joubert syndrome. Sources: Literature |
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| Skeletal dysplasia v0.259 | SOX8 |
Paul De Fazio gene: SOX8 was added gene: SOX8 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088 Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related Review for gene: SOX8 was set to RED gene: SOX8 was marked as current diagnostic Added comment: Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces. Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets. Sources: Literature |
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| Skeletal dysplasia v0.254 | CSGALNACT1 |
Zornitza Stark gene: CSGALNACT1 was added gene: CSGALNACT1 was added to Skeletal dysplasia. Sources: Expert Review Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CSGALNACT1 were set to 31705726; 31325655 Phenotypes for gene: CSGALNACT1 were set to Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870 Review for gene: CSGALNACT1 was set to GREEN Added comment: Four families reported. Sources: Expert Review |
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| Skeletal dysplasia v0.252 | MAB21L2 |
Zornitza Stark gene: MAB21L2 was added gene: MAB21L2 was added to Skeletal dysplasia. Sources: Expert Review Mode of inheritance for gene: MAB21L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAB21L2 were set to 24906020; 25719200; 31037784; 30375740; 30073347; 26116559 Phenotypes for gene: MAB21L2 were set to Microphthalmia/coloboma and skeletal dysplasia syndrome, MIM# 615877 Review for gene: MAB21L2 was set to GREEN Added comment: More than 7 unrelated families reported with microphthalmia/anophthalmia/coloboma and rhizomelia. Several individuals with the c.151C > T (p.Arg51Cys) variant also had ID. One family reported with eye phenotype and bi-allelic missense variants, LIMITED evidence for bi-allelic disease. Three different animal models support gene-disease association. Sources: Expert Review |
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| Skeletal dysplasia v0.241 | PLK4 |
Zornitza Stark changed review comment from: At least 3 unrelated families reported with autosomal recessive developmental disorder characterised by delayed psychomotor development, visual impairment, and microcephaly.; to: At least 3 unrelated families reported with autosomal recessive developmental disorder characterised by delayed psychomotor development, visual impairment, and microcephaly. Short stature but no specific skeletal abnormalities. |
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| Skeletal dysplasia v0.241 | PHF6 |
Zornitza Stark changed review comment from: Clinical features are quite variable, with the most consistent features being initial hypotonia, mild to moderate impaired intellectual development, large fleshy ears, underdeveloped genitalia, gynecomastia, truncal obesity, tapering fingers, and shortening of the fourth and fifth toes. Heterozygous females may have a milder similar clinical phenotype, which can include hypothyroidism; however, many carrier females appear unaffected. More than 20 families reported.; to: Clinical features are quite variable, with the most consistent features being initial hypotonia, mild to moderate impaired intellectual development, large fleshy ears, underdeveloped genitalia, gynecomastia, truncal obesity, tapering fingers, and shortening of the fourth and fifth toes. Heterozygous females may have a milder similar clinical phenotype, which can include hypothyroidism; however, many carrier females appear unaffected. More than 20 families reported. Abnormal skeletal features including thickened calvarium and abnormal vertebrae reported. |
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| Skeletal dysplasia v0.238 | IFT74 |
Naomi Baker gene: IFT74 was added gene: IFT74 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IFT74 were set to PMID:37315079 Phenotypes for gene: IFT74 were set to Jeune syndrome (MONDO:0018770), IFT74-related Review for gene: IFT74 was set to GREEN Added comment: Five individuals from four families reported. A homozygous exon 2 deletion was identified in two families, and splice variants were identified in the other two families (with minigene experiments demonstrating an effect on splicing of the non-canonical/deep intronic splice variants). Authors also characterised three mouse Ift74 alleles, with phenotypes ranging from a severe mid gestational lethal phenotype in the Ift74Tm1d out of frame exon 3 deletion allele, a post-natal lethal phenotype in the Ift74Tm1a exon 2 skip allele, to no detectable phenotype in Ift74Tm1b in frame exon 3 deletion allele. Sources: Literature |
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| Skeletal dysplasia v0.229 | DDRGK1 |
Achchuthan Shanmugasundram gene: DDRGK1 was added gene: DDRGK1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: DDRGK1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DDRGK1 were set to 28263186; 35377455; 35670300; 36243336 Phenotypes for gene: DDRGK1 were set to Spondyloepimetaphyseal dysplasia, Shohat type, OMIM:602557 Review for gene: DDRGK1 was set to GREEN Added comment: Comment on gene classification: This gene should be rated GREEN as it has been associated with Spondyloepimetaphyseal dysplasia, Shohat type from seven unrelated cases from multiple ethnicities and supported by functional studies. PMID:28263186 reported six individuals from three different families of Iraqi Jewish descent (three patients from family 1 and one individual each from families 2-4) identified with homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK1 and presented with Shohat-type spondyloepimetaphyseal dysplasia (SEMD). It is a skeletal dysplasia that affects cartilage development. PMID: 35670300 reported two unrelated cases of Moroccan descent identified with homozygous missense variant c.406G>A and presented with SEMD. PMID:36243336 reported an Omani female patient identified with the same homozygous variant as the Iraqi cases and was reported with SEMD. In addition, studies on both zebrafish and mouse models confirms the physiological role of DDRGK1 in the development and maintenance of the growth plate cartilage and deficiency of DDRGK1 recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD (PMID:28263186; PMID:35377455). This gene has been associated with relevant phenotype in OMIM (MIM #602557), but not in Gene2Phenotype. Sources: Literature |
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| Skeletal dysplasia v0.227 | CBFB |
Ain Roesley gene: CBFB was added gene: CBFB was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: CBFB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CBFB were set to 36241386 Phenotypes for gene: CBFB were set to cleidocranial dysplasia (MONDO#0007340), CBFB-related Penetrance for gene: CBFB were set to Complete Review for gene: CBFB was set to GREEN gene: CBFB was marked as current diagnostic Added comment: 5 families with 8 individuals, including 2 de novos and 1 intragenic exon 4 deletion In 1 family, the mother did not report skeletal concerns but had dental abnormalities during childhood Sources: Literature |
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| Skeletal dysplasia v0.219 | FAM20B |
Zornitza Stark gene: FAM20B was added gene: FAM20B was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: FAM20B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM20B were set to 30847897; 30105814; 22732358; 27405802 Phenotypes for gene: FAM20B were set to Desbuquois dysplasia MONDO:0015426 Review for gene: FAM20B was set to AMBER Added comment: Two siblings from a single family with neonatal short limb dysplasia resembling Desbuquois dysplasia. One of the siblings underwent genetic testing and compound heterozygous variants were identified in FAM20B ((NM_014864: c.174_178delTACCT p.T59Afs*19/c.1038delG p.N347Mfs*4). Multiple mouse models reported with skeletal abnormalities. Sources: Literature |
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| Skeletal dysplasia v0.217 | EXOC6B |
Bryony Thompson gene: EXOC6B was added gene: EXOC6B was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: EXOC6B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC6B were set to 26669664; 30284759; 36150098 Phenotypes for gene: EXOC6B were set to Spondyloepimetaphyseal dysplasia with joint laxity MONDO:0019675 Review for gene: EXOC6B was set to GREEN Added comment: 6 affected individuals from 4 families, and supporting assays in patient cells PMID: 26669664 - 2 brothers with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones from a consanguineous family, with a homozygous nonsense variant [c.906T>A/p.(Tyr302*)] PMID: 30284759 - 2 sisters with dislocations of the hips and knees, long slender fingers with distal tapering, significant motor disability but normal (older sister) or low-normal intelligence (younger sister), with a homozygous in-frame deletion of exons 9-20 PMID: 36150098 - 2 unrelated probands from consanguineous families, one with a homozygous frameshift exon 20 deletion and one with a homozygous nonsense variant (c.401T>G p.Leu134Ter). Function assessment of patient fibroblast cell lines indicated abrogation of exocytosis leading to impaired primary ciliogenesis Sources: Literature |
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| Skeletal dysplasia v0.209 | ACVR1 |
Zornitza Stark changed review comment from: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner. Multiple unrelated families reported. The R206H variant is recurrent. Note variants in this gene are also associated with congenital heart disease, PMID 29089047.; to: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner. Multiple unrelated families reported. The R206H variant is recurrent. Clinical trial with palovarotene. Note variants in this gene are also associated with congenital heart disease, PMID 29089047. |
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| Skeletal dysplasia v0.205 | MPDU1 |
Zornitza Stark changed review comment from: More than 5 unrelated families reported. Prominent ichthyosis reported in some, in addition to neurological features including DD/ID, seizures, hypotonia. Some reported with features overlapping dystroglycanopathy, including raised CK.; to: More than 5 unrelated families reported. Prominent ichthyosis reported in some, in addition to neurological features including DD/ID, seizures, hypotonia. Some reported with features overlapping dystroglycanopathy, including raised CK. Listed in the skeletal nosology paper as a condition resembling storage diseases, occasional reports of severe short stature. |
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| Skeletal dysplasia v0.180 | GINS3 |
Zornitza Stark gene: GINS3 was added gene: GINS3 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GINS3 were set to 35603789 Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related Review for gene: GINS3 was set to GREEN Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model. Sources: Literature |
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| Skeletal dysplasia v0.175 | MECOM |
Chirag Patel gene: MECOM was added gene: MECOM was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: MECOM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MECOM were set to PMID: 35219593, 26581901, 29519864 Phenotypes for gene: MECOM were set to Radioulnar synostosis with amegakaryocytic thrombocytopenia 2, OMIM # 616738; Radioulnar synostosis without hematological aberration, no OMIM # Review for gene: MECOM was set to GREEN Added comment: Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 -Multiple affected families reported Radioulnar synostosis (RUS) without hematological aberration -8 families with RUS and no identifiable hematological abnormalities -WES identified unique missense variants in MECOM -6 families had variants in residue R781, 2 other variants included I783T and Q777E. All variants clustered within the ninth zinc finger motif of EVI1. -Functional experiments showed that MECOM R781C led to alterations in TGF-β–mediated transcriptional responses. Sources: Literature |
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| Skeletal dysplasia v0.153 | SEMA3A |
Krithika Murali gene: SEMA3A was added gene: SEMA3A was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: SEMA3A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: SEMA3A were set to 28075028; 33369061; 20301509; 21059704; 24124006; 22927827 Phenotypes for gene: SEMA3A were set to {Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897; congenital heart disease; short stature Review for gene: SEMA3A was set to GREEN Added comment: Heterozygous variants associated with isolated GnRH deficiency with or without anosmia (Kallman syndrome like). More severe phenotype with biallelic SEMA3A variants reported including postnatal short stature and congenital heart defects in 3/3 published, unrelated individuals. PMID 33369061 Gileta et al 2021 - report x1 patient. Female proband was compound heterozygote for a nonsense variant and a multiexonic deletion of SEMA3A. Presents with postnatal short stature, congenital cardiac anomalies, dysmorphic features, hypogonadotrophic hypogonadism and anosmia. PMID 28075028 Baumann et al 2017 - report x1 patient. Homozygous LoF variants identified in a proband from a consanguineous Turkish family. Noted at birth to have a high-positioned scapulae, deformed ribs and a lateral clavicular hook. The patient also had upper/lower limb contractures and aberrant right subclavian artery. Mild facial dysmorphism, micropenis and hypogonadotrophic hypogonadism also noted in the first week of life. Postnatal short stature (length 50cm at term birth) PMID 24124006 Hofmann et al 2013 - first reported biallelic variants in a proband with postnatal short stature, skeletal anomalies of the thorax, congenital heart defect and camptodactyly Sources: Literature |
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| Skeletal dysplasia v0.152 | ARSK |
Paul De Fazio gene: ARSK was added gene: ARSK was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARSK were set to 34916232; 32856704 Phenotypes for gene: ARSK were set to Mucopolysaccharidosis MONDO:0019249, ARSK-related Review for gene: ARSK was set to GREEN gene: ARSK was marked as current diagnostic Added comment: 4 individuals from 2 unrelated consanguineous families reported with a homozygous missense and an NMD-predicted nonsense variant, who had features of mucopolysaccharidosis such as short stature, coarse facial features and dysostosis multiplex. Urinary GAG excretion was normal by conventional methods, but LC-MS/MS in 2 individuals revealed an increase in specific dermatan sulfate-derived disaccharides. Functional studies showed reduced protein levels and reduced enzyme activity for the nonsense and missense variant respectively. A mouse model also shows a mucopolysaccharidosis phenotype, albeit milder. Rated green (2 families, functional evidence, mouse model). Sources: Literature |
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| Skeletal dysplasia v0.150 | SMAD6 |
Chris Richmond gene: SMAD6 was added gene: SMAD6 was added to Skeletal dysplasia. Sources: Expert Review Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMAD6 were set to 31138930 Phenotypes for gene: SMAD6 were set to 179300 Penetrance for gene: SMAD6 were set to Incomplete Review for gene: SMAD6 was set to GREEN gene: SMAD6 was marked as current diagnostic Added comment: Yang et al. (2019) performed exome sequencing on 117 patients with sporadic RUS and found significant enrichment for loss-of-function variants in the SMAD6 gene. Identified 22 SMAD6 rare variants (with a minor allele frequency of less than 0.0001) that occurred in 22 nonsyndromic RUS patients. Logistic regression showed that SMAD6 loss-of-function variants were significantly associated with increased risk of nonsyndromic RUS (OR 430; 95% CI 237.5-780.1; p less than 0.000001). Some inherited from unaffected parents. Sources: Expert Review |
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| Skeletal dysplasia v0.140 | HHAT | Zornitza Stark edited their review of gene: HHAT: Added comment: Additional family reported, with severe microcephaly, skeletal dysplasia and sex reversal phenotype.; Changed rating: GREEN; Changed publications: 24784881, 30912300, 33749989; Changed phenotypes: Nivelon-Nivelon-Mabille syndrome 600092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.138 | PRKG2 | Zornitza Stark edited their review of gene: PRKG2: Added comment: PMID 34782440: 4 further families reported.; Changed publications: 33106379, 34782440 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.133 | SIK3 |
Krithika Murali gene: SIK3 was added gene: SIK3 was added to Skeletal dysplasia. Sources: Expert list,Literature Mode of inheritance for gene: SIK3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SIK3 were set to 30232230; 22318228 Phenotypes for gene: SIK3 were set to ?Spondyloepimetaphyseal dysplasia, Krakow type - #618162 Review for gene: SIK3 was set to AMBER Added comment: Biallelic SIK3 variants reported in 2 siblings from a consanguineous family with an uncharacterised skeletal dysplasia. Radiographic features included widened/flared metaphyses with irregular ossifications, motheaten long bones, fragmentation of the proximal metacarpals, rounded vertebral bodies, and a distinctive transverse gap seen in the tibias. In addition to the skeletal phenotype, the siblings manifested significant developmental delay with brain MRI abnormalities, a severe unclassified immunodeficiency, and normal parathyroid hormone concentration with mild hypercalcemia. One sibling had a more severe phenotype, particularly immunodeficiency, and died of Epstein-Barr virus induced small muscle cancer at 10 years of age. Mouse models support impaired chondrocyte development with skeletal dysplasia phenotype. Sources: Expert list, Literature |
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| Skeletal dysplasia v0.131 | STT3A |
Elena Savva gene: STT3A was added gene: STT3A was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: STT3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: STT3A were set to PMID: 34653363; 23842455; 30701557; 28424003 Phenotypes for gene: STT3A were set to Congenital disorder of glycosylation, type Iw MIM#615596 Mode of pathogenicity for gene: STT3A was set to Other Review for gene: STT3A was set to GREEN Added comment: ID/DD reported in all cases (at least 7 individuals from 3 unrelated families, with 2 different homozygous variants in STT3A) PMID: 34653363 - 16 patients from 9 families with new AD mode of inheritance (both de novo and inherited). All variants were missense within/around acritical active/catalytic sites. Patients aged 3-55yo, with children noted to be "healthy" until reaching young adulthood Clinical features include dysmorphic features, macrocephaly (6/16), mild-moderate ID/DD (10/16), short stature (8/16), skeletal abnormalities (10/16), muscle cramps (7/16). Functional studies verifies AR disease is caused by LOF variants, whereas the AD variants cause DN proven by cotransfection in WT yeast resulting in impaired glycosylation (protein levels unchanged). Sources: Literature |
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| Skeletal dysplasia v0.122 | LRRK1 |
Zornitza Stark gene: LRRK1 was added gene: LRRK1 was added to Skeletal dysplasia. Sources: Expert Review Mode of inheritance for gene: LRRK1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRK1 were set to 27829680; 27055475; 31571209; 32119750 Phenotypes for gene: LRRK1 were set to Osteosclerotic metaphyseal dysplasia (OSMD) (OMIM: 615198) Review for gene: LRRK1 was set to GREEN Added comment: At least 4 unrelated families reported. Sources: Expert Review |
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| Skeletal dysplasia v0.119 | ARID1B | Bryony Thompson changed review comment from: Skeletal limb anomalies, spinal anomalies, and short stature have been reported as a feature of the condition. >3 cases reported.; to: Skeletal limb anomalies, spinal anomalies, and short stature have been reported as a feature of the condition. >3 cases reported, at least one case identified in a skeletal dysplasia cohort. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.118 | ARID1B | Bryony Thompson changed review comment from: Skeletal limb anomalies, spinal anomalies, and short stature have been reported as a feature of the condition. > cases reported.; to: Skeletal limb anomalies, spinal anomalies, and short stature have been reported as a feature of the condition. >3 cases reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.115 | ARID1A | Bryony Thompson changed review comment from: At least 5 cases have been reported with skeletal anomalies as a feature of the condition. Mosaicism is very common for the gene.; to: At least 5 cases have been reported with skeletal anomalies (brachydactyly and polydactyly) as a feature of the condition. Mosaicism is very common for the gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.104 | LAMA5 |
Bryony Thompson gene: LAMA5 was added gene: LAMA5 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: LAMA5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LAMA5 were set to 33242826 Phenotypes for gene: LAMA5 were set to Bent bone dysplasia Review for gene: LAMA5 was set to RED Added comment: A single family with 3 affected siblings with biallelic variants, and some supporting in vitro functional assays. Sources: Literature |
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| Skeletal dysplasia v0.91 | CHST11 |
Zornitza Stark gene: CHST11 was added gene: CHST11 was added to Skeletal dysplasia. Sources: Expert list Mode of inheritance for gene: CHST11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHST11 were set to 26436107; 29514872 Phenotypes for gene: CHST11 were set to Osteochondrodysplasia, brachydactyly, and overlapping malformed digits, MIM# 618167 Review for gene: CHST11 was set to AMBER Added comment: Two unrelated families reported, note one had a homozygous deletion. Sources: Expert list |
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| Skeletal dysplasia v0.89 | MIA3 |
Zornitza Stark gene: MIA3 was added gene: MIA3 was added to Skeletal dysplasia. Sources: Expert list Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIA3 were set to 32101163; 33778321 Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269 Review for gene: MIA3 was set to AMBER Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported, homozygous variant affecting splicing. Mouse model has absence of bone mineralization. Sources: Expert list |
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| Skeletal dysplasia v0.85 | DONSON |
Zornitza Stark gene: DONSON was added gene: DONSON was added to Skeletal dysplasia. Sources: Expert Review Mode of inheritance for gene: DONSON was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DONSON were set to 28191891; 28630177; 28191891 Phenotypes for gene: DONSON were set to Microcephaly, short stature, and limb abnormalities, MIM# 617604; Microcephaly-micromelia syndrome, MIM# 251230 Review for gene: DONSON was set to GREEN Added comment: MISSLA, MIM# 617604 is an autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly (-2.4 to -10.7 SD), variable short stature (-1.2 SD to -4 SD, although 1 individual had stature of -8.4 SD), and limb abnormalities mainly affecting the upper limb and radial ray. Affected individuals typically have mild intellectual disability, but may have normal development. At least 20 unrelated families reported. Microcephaly-micromelia syndrome (MIM#251230), is a more severe disorder that usually results in intrauterine or perinatal death. Multiple affected individuals reported with homozygous c.1047-9A-G variant, from different ethnicities. Sources: Expert Review |
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| Skeletal dysplasia v0.83 | EN1 |
Zornitza Stark changed review comment from: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype. Sources: Literature; to: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype. An additional fourth individual had cerebellar hypoplasia in addition to the skeletal phenotype, and a bi-allelic LoF variant. Sources: Literature |
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| Skeletal dysplasia v0.82 | EN1 |
Zornitza Stark gene: EN1 was added gene: EN1 was added to Skeletal dysplasia. Sources: Literature SV/CNV, 5'UTR tags were added to gene: EN1. Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EN1 were set to 33568816 Phenotypes for gene: EN1 were set to ENDOVE syndrome, limb-only type, MIM# 619217 Review for gene: EN1 was set to GREEN Added comment: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype. Sources: Literature |
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| Skeletal dysplasia v0.71 | SCUBE3 |
Zornitza Stark gene: SCUBE3 was added gene: SCUBE3 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: SCUBE3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCUBE3 were set to 33308444 Phenotypes for gene: SCUBE3 were set to Short stature; skeletal abnormalities; craniofacial abnormalities; dental anomalies Review for gene: SCUBE3 was set to GREEN Added comment: Eighteen affected individuals from nine unrelated families reported with a consistent phenotype characterised by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. Mouse model recapitulated phenotype. Sources: Literature |
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| Skeletal dysplasia v0.70 | FBLN1 |
Zornitza Stark changed review comment from: Single association to disease published in literature - reciprocal translocation region t(12;22)(p11.2;q13.3) found in the family. The breakpoint was located in the intron between the last 2 exons of the FBLN1-D splice variant isoform (exons 19-20). Additional pathogenic missense in ClinVar, but a research finding and inherited; to: Single association of mono-allelic variants to disease published in literature - reciprocal translocation region t(12;22)(p11.2;q13.3) found in the family. The breakpoint was located in the intron between the last 2 exons of the FBLN1-D splice variant isoform (exons 19-20). Additional pathogenic missense in ClinVar, but a research finding and inherited. Single report of homozygous missense in a family with syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. |
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| Skeletal dysplasia v0.67 | HHAT |
Zornitza Stark gene: HHAT was added gene: HHAT was added to Skeletal dysplasia. Sources: Expert list Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HHAT were set to 24784881; 30912300 Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome 600092 Review for gene: HHAT was set to AMBER Added comment: Two unrelated families reported. Clinical features include progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Variable features include infantile-onset seizures, dwarfism, generalized chondrodysplasia, and micromelia. Sources: Expert list |
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| Skeletal dysplasia v0.65 | TONSL |
Zornitza Stark gene: TONSL was added gene: TONSL was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: TONSL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TONSL were set to 30773277; 30773278; 32959051 Phenotypes for gene: TONSL were set to Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510; spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068 Review for gene: TONSL was set to GREEN Added comment: Associated with Spondyloepimetaphyseal dysplasia, sponastrime type MIM#271510 (AR) in OMIM. PMID: 30773277 - Burrage et al 2019 - identified, using WES or Sanger sequencing, compound heterozygous variants in TONSL in 9 individuals (8 families) with SPONASTRIME dysplasia. 4 other probands with SPONASTRIME dysplasia did not have biallelic variants in TONSL or in MMS22L, but two of them did have a single heterozygous variants in TONSL. The authors say they cannot exclude deep intronic, promotor variants or large intragenic rearrangements/deletions in these patients. An additional 4 individuals (3 families) with short stature of varied severity and spondylometaphyseal dysplasia with or without immunologic and hematologic abnormalities were also found to have compound heterozygous variants in TONSL. PMID: 30773278 - Chang et al 2019 - Using WES they identified homozygous or compound heterozygous TONSL variants in 10 of 13 individuals (9 families) with SPONASTRIME dysplasia. PMID: 32959051 - Micale et al 2020 - report a 9-year-old Italian girl with typical SPONASTRIME dysplasia who was found to have two novel missense variants in TONSL. Each parent was heterozygous for one of the variants. Both variants were found to be very rare in the gnomad database. Patient-derived fibroblasts show increased levels of spontaneous chromosomal breaks, reduced cell proliferation and enhanced apoptosis. Sources: Literature |
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| Skeletal dysplasia v0.55 | WDPCP | Zornitza Stark changed review comment from: Two families reported; the first one with a BBS phenotype, and in the second one affected individual had polysyndactyly and tongue hamartomas, so phenotype consistent with OFD rather than BBS.; to: Four families reported with ciliopathy phenotypes, including BBS, OFD, syndromic retinopathy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.47 | MBTPS1 |
Zornitza Stark gene: MBTPS1 was added gene: MBTPS1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013 Phenotypes for gene: MBTPS1 were set to Skeletal dysplasia Review for gene: MBTPS1 was set to GREEN Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature. Sources: Literature |
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| Skeletal dysplasia v0.45 | MTX2 |
Zornitza Stark gene: MTX2 was added gene: MTX2 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTX2 were set to 32917887 Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification Review for gene: MTX2 was set to GREEN Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Sources: Literature |
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| Skeletal dysplasia v0.38 | GNPNAT1 |
Zornitza Stark gene: GNPNAT1 was added gene: GNPNAT1 was added to Skeletal dysplasia. Sources: Expert list Mode of inheritance for gene: GNPNAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GNPNAT1 were set to 32591345 Phenotypes for gene: GNPNAT1 were set to Rhizomelic skeletal dysplasia Review for gene: GNPNAT1 was set to AMBER Added comment: PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype. Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation. Additional cases required to validate pathogenicity of GNPNAT1. Sources: Expert list |
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| Skeletal dysplasia v0.37 | PLCB3 |
Zornitza Stark gene: PLCB3 was added gene: PLCB3 was added to Skeletal dysplasia. Sources: Expert list Mode of inheritance for gene: PLCB3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLCB3 were set to 29122926 Phenotypes for gene: PLCB3 were set to Spondylometaphyseal dysplasia with corneal dystrophy, MIM# 618961 Review for gene: PLCB3 was set to RED Added comment: Single consanguineous family reported. Sources: Expert list |
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| Skeletal dysplasia v0.29 | COG4 |
Chirag Patel changed review comment from: Saul-Wilson syndrome (AD) 14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like) All have a recurrent de novo heterozygous missense variant (p.Gly516Arg) Congenital disorder of glycosylation, type IIj (AR) Sources: Literature; to: Saul-Wilson syndrome (AD) 14 patients reported with DD, skeletal dysplasia changes, cataracts, and growth retardation (progeriod like) All have a recurrent de novo heterozygous missense variant (p.Gly516Arg) Congenital disorder of glycosylation, type IIj (AR) Sources: Literature |
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| Skeletal dysplasia v0.29 | COG4 |
Chirag Patel gene: COG4 was added gene: COG4 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: COG4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: COG4 were set to PMID: 31949312; 30290151 Phenotypes for gene: COG4 were set to Saul-Wilson syndrome, OMIM #618150; Congenital disorder of glycosylation, type IIj, OMIM #613489 Review for gene: COG4 was set to GREEN Added comment: Saul-Wilson syndrome (AD) 14 patients reported with DD, skeletal changes, cataracts, and growth retardation (progeriod like) All have a recurrent de novo heterozygous missense variant (p.Gly516Arg) Congenital disorder of glycosylation, type IIj (AR) Sources: Literature |
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| Skeletal dysplasia v0.14 | PKDCC |
Zornitza Stark gene: PKDCC was added gene: PKDCC was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: PKDCC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PKDCC were set to 30478137; 19097194 Phenotypes for gene: PKDCC were set to Rhizomelia; dysmorphism Review for gene: PKDCC was set to AMBER Added comment: Two unrelated consanguineous families reported with different homozygous variants Pre-existing mouse model has similar phenotype Sources: Literature |
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| Skeletal dysplasia v0.11 | MIR140 |
Chris Richmond gene: MIR140 was added gene: MIR140 was added to Skeletal dysplasia. Sources: Expert Review Mode of inheritance for gene: MIR140 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MIR140 were set to 30804514; 31633310 Phenotypes for gene: MIR140 were set to 618618 Penetrance for gene: MIR140 were set to unknown Mode of pathogenicity for gene: MIR140 was set to Other Review for gene: MIR140 was set to GREEN Added comment: Single clinical paper (30804514) reports variant in affected mother and child (de novo in mother) and in a separate unrelated female (de novo) with spondylo-epiphyseal dysplasia. Mouse model (21576357) deletion of gene causes impaired longitudinal bone growth. Separate mouse model studies by same authors as clinical paper above (30804514) showed phenotype of mice with same mutation in this gene consistent with the skeletal dysplasia features of patients with the n.24A-G mutation, suggestive of neomorphic effects (mutation produces both loss-of-function and gain-of-function effects.) Sources: Expert Review |
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| Skeletal dysplasia v0.9 | RSPRY1 |
Zornitza Stark gene: RSPRY1 was added gene: RSPRY1 was added to Skeletal dysplasia. Sources: Expert list Mode of inheritance for gene: RSPRY1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RSPRY1 were set to 26365341 Phenotypes for gene: RSPRY1 were set to Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, 616585 Review for gene: RSPRY1 was set to AMBER Added comment: Two unrelated individuals reported, some functional evidence. Sources: Expert list |
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| Skeletal dysplasia v0.4 | MESD |
Zornitza Stark gene: MESD was added gene: MESD was added to Skeletal dysplasia. Sources: Other Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MESD were set to 31564437 Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX, MIM# 618644 Review for gene: MESD was set to GREEN Added comment: Five unrelated families reported. Sources: Other |
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| Skeletal dysplasia v0.1 | PISD |
Zornitza Stark gene: PISD was added gene: PISD was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: PISD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PISD were set to 30488656; 31263216; 30858161 Phenotypes for gene: PISD were set to Spondylometaphyseal dysplasia with large epiphyses Review for gene: PISD was set to AMBER Added comment: Two unrelated probands from non-consanguineous families identified as having the same homozygous variant; some functional data. Note there was some regions of homozygosity identified, indicative of distant relatedness and therefore founder effect. Three other families reported with bi-allelic variants in this gene in 2019 and a multi-system disorder including short stature, but skeletal findings not as well characterised as in this paper. Sources: Literature |
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| Skeletal dysplasia v0.0 | TOPORS |
Zornitza Stark gene: TOPORS was added gene: TOPORS was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory Mode of inheritance for gene: TOPORS was set to |
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| Skeletal dysplasia v0.0 | PIR |
Zornitza Stark gene: PIR was added gene: PIR was added to Skeletal dysplasia. Sources: Expert Review Red Mode of inheritance for gene: PIR was set to Unknown Publications for gene: PIR were set to 16183656; 19766747 Phenotypes for gene: PIR were set to Osteoporosis |
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| Skeletal dysplasia v0.0 | HDAC5 |
Zornitza Stark gene: HDAC5 was added gene: HDAC5 was added to Skeletal dysplasia. Sources: Expert Review Red,Expert list Mode of inheritance for gene: HDAC5 was set to Unknown Publications for gene: HDAC5 were set to 26723575 Phenotypes for gene: HDAC5 were set to osteoporosis |
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| Skeletal dysplasia v0.0 | FGF8 |
Zornitza Stark gene: FGF8 was added gene: FGF8 was added to Skeletal dysplasia. Sources: Expert Review Red Mode of inheritance for gene: FGF8 was set to Unknown Publications for gene: FGF8 were set to 24569166 Phenotypes for gene: FGF8 were set to Numerous variants reported in Hypogonadotropic hypogonadism 6 with or without anosmia 612702, but this phenotype is not relevant to this panel. |
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| Skeletal dysplasia v0.0 | WNT1 |
Zornitza Stark gene: WNT1 was added gene: WNT1 was added to Skeletal dysplasia. Sources: NHS GMS,Radboud University Medical Center, Nijmegen,Expert,Expert Review Green Mode of inheritance for gene: WNT1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Phenotypes for gene: WNT1 were set to OI/osteoporosis; osteogenesis imperfecta; Osteogenesis imperfecta, type XV, 615220; {Osteoporosis, early-onset, susceptibility to, autosomal dominant}, 615221 |
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| Skeletal dysplasia v0.0 | SLC35C1 |
Zornitza Stark gene: SLC35C1 was added gene: SLC35C1 was added to Skeletal dysplasia. Sources: Other,Expert Review Green Mode of inheritance for gene: SLC35C1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC35C1 were set to 12476046; 11326280 Phenotypes for gene: SLC35C1 were set to GDP-fucose transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways); Congenital disorder of glycosylation, type IIc 266265 |
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| Skeletal dysplasia v0.0 | SLC34A1 |
Zornitza Stark gene: SLC34A1 was added gene: SLC34A1 was added to Skeletal dysplasia. Sources: Other,Expert Review Green Mode of inheritance for gene: SLC34A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SLC34A1 were set to 12324554; 25050900; 9560283 Phenotypes for gene: SLC34A1 were set to Nephrolithiasis/osteoporosis, hypophosphatemic, 1, 612286 |
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| Skeletal dysplasia v0.0 | SERPINF1 |
Zornitza Stark gene: SERPINF1 was added gene: SERPINF1 was added to Skeletal dysplasia. Sources: NHS GMS,Radboud University Medical Center, Nijmegen,Expert Review Green,Expert,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: SERPINF1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SERPINF1 were set to OI/osteoporosis; osteogenesis imperfecta; Osteogenesis Imperfecta, Recessive; Osteogenesis imperfecta, type VI, 613982 |
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| Skeletal dysplasia v0.0 | POR |
Zornitza Stark gene: POR was added gene: POR was added to Skeletal dysplasia. Sources: Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,Expert Review Green,UKGTN,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: POR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: POR were set to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571 |
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| Skeletal dysplasia v0.0 | PLS3 |
Zornitza Stark gene: PLS3 was added gene: PLS3 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review,Expert Review Green Mode of inheritance for gene: PLS3 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: PLS3 were set to Bone mineral density QTL18, osteoporosis 300910 |
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| Skeletal dysplasia v0.0 | MATN3 |
Zornitza Stark gene: MATN3 was added gene: MATN3 was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,NHS GMS,Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: MATN3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MATN3 were set to 16199550; 16287128; 15121775; 30080953; 11479597 Phenotypes for gene: MATN3 were set to MED; Multiple Epiphyseal Dysplasia, Dominant; Disproportionate Short Stature; Spondyloepimetaphyseal dysplasia, 608728; Epiphyseal dysplasia, multiple, 5, 607078; {Osteoarthritis susceptibility 2}, 140600; multiple epiphyseal dysplasia |
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| Skeletal dysplasia v0.0 | LRP5 |
Zornitza Stark gene: LRP5 was added gene: LRP5 was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,NHS GMS,Expert,Expert Review Green Mode of inheritance for gene: LRP5 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Phenotypes for gene: LRP5 were set to Exudative vitreoretinopathy 4 601813; Osteoporosis-pseudoglioma syndrome 259770; [Bone mineral density variability 1] 601884; {Osteoporosis} 166710; van Buchem disease, type 2 607636; Osteopetrosis, autosomal dominant 1 607634; Hyperostosis, endosteal 144750; Osteosclerosis 144750 |
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| Skeletal dysplasia v0.0 | GHR |
Zornitza Stark gene: GHR was added gene: GHR was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,NHS GMS,Radboud University Medical Center, Nijmegen,Expert Review Green Mode of inheritance for gene: GHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: GHR were set to increased responsiveness to growth hormone 604271; {Hypercholesterolemia, familial, modification of}, 143890; Short stature, 604271; Proportionate Short Stature/Small for Gestational Age; Growth hormone insensitivity; Increased responsiveness to growth hormone; Laron dwarfism, 262500 |
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| Skeletal dysplasia v0.0 | DDR2 |
Zornitza Stark gene: DDR2 was added gene: DDR2 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: DDR2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DDR2 were set to Spondylometaepiphyseal dysplasia, short limb-hand type 271665; Spondylometaepiphyseal dysplasia, short limb-hand type 271665, at least 3 cases reported |
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| Skeletal dysplasia v0.0 | ANO5 |
Zornitza Stark gene: ANO5 was added gene: ANO5 was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,NHS GMS,Expert Review Green Mode of inheritance for gene: ANO5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ANO5 were set to Disproportionate Short Stature; Osteogenesis Imperfecta and Decreased Bone Density; Gnatodiaphyseal dysplasia; skeletal dysplasias |
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