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| Callosome v0.554 | TMEM184B |
Lucy Spencer gene: TMEM184B was added gene: TMEM184B was added to Callosome. Sources: Literature Mode of inheritance for gene: TMEM184B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TMEM184B were set to 39006436 Phenotypes for gene: TMEM184B were set to Neurodevelopmental disorder (MONDO:0700092), TMEM184B-related Review for gene: TMEM184B was set to GREEN Added comment: A cohort of 6 patients with developmental delay (5/6), corpus callosum hypoplasia (4/6), microcephaly (1/6), seizures (3/6), and ID (2/6). 2 patients also had gastrointestinal motility disruption. All 6 have de novo variants in TMEM184B, 5 missense 1 canonical splice. 1 of the missense variants has 35 hets in gnomad but the rest are absent. The authors also say they are aware of a 7th patient with overlapping features by personal communication. A knockout zebrafish model showed a dose dependent reduction in head size and body length in larvae. Knock-in of 2 of the missense variants also showed head size and body length reduction, but the other missense did not. However the other three missense failed to rescue the phenotype of a knockout zebrafish while WT and a negative control did. The authors suggest the first 2 variants are dominant negative while the latter three and loss of function. The splice variant was shown to cause exon 7 skipping which is out of frame. Transfection of the missense and splice variants in HEK293T cells showed that all but 1 had reduced TMEM184B protein levels. Sources: Literature |
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| Callosome v0.523 | SRPK3 |
Zornitza Stark gene: SRPK3 was added gene: SRPK3 was added to Callosome. Sources: Literature Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SRPK3 were set to 38429495; 39073169 Phenotypes for gene: SRPK3 were set to Neurodevelopmental disorder, MONDO:0700092, SRPK3-related Review for gene: SRPK3 was set to GREEN Added comment: PMID 39073169: 9 individuals from 5 unrelated families reported with 4 missense and 1 putative truncating variant and a neurodevelopmental phenotype. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Supportive animal model data (mouse and zebrafish). Sources: Literature |
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| Callosome v0.516 | SNF8 |
Chern Lim gene: SNF8 was added gene: SNF8 was added to Callosome. Sources: Literature Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNF8 were set to 38423010 Phenotypes for gene: SNF8 were set to Severe developmental delay, epileptic encephalopathy, brain MRI abnormality; intellectual disability, childhood-onset optic atrophy, ataxia Review for gene: SNF8 was set to GREEN gene: SNF8 was marked as current diagnostic Added comment: PMID: 38423010 - Nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8. In total, three putative LoF variants and four missense variants were identified. - The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. - Functional studies using fibroblasts derived from patients and zebrafish model showed LoF is the disease mech. Sources: Literature |
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| Callosome v0.0 | BRAF |
Zornitza Stark gene: BRAF was added gene: BRAF was added to Corpus callosum agenesis, Callosome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: BRAF was set to Unknown |
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