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| Paediatric disorders - additional genes v8.17 | COMMD4 |
Alexandra Njegic gene: COMMD4 was added gene: COMMD4 was added to Paediatric disorders - additional genes. Sources: Literature Mode of inheritance for gene: COMMD4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COMMD4 were set to 40601774; 39937864 Phenotypes for gene: COMMD4 were set to Ritscher-Schinzel Syndrome Penetrance for gene: COMMD4 were set to unknown Mode of pathogenicity for gene: COMMD4 was set to Other Review for gene: COMMD4 was set to AMBER Added comment: PMID: 40601774 identified a homozygous missense variant in COMMD4 (p.Leu41Arg (L41R)) which was shown in vitro to decrease the steady-state abundance of COMMD4 when compared with the parental cells (shown with western blot analysis on HEK 293T cells carrying a-L41R knock-in, probands deceased and therefore no patient-derived sample available); knock-in cells also displayed reduced cell surface abundance of ITGB1 and LRP1 vs. wild-type cells in Western blotting, suggesting a defect in Commander-mediated cargo recycling. Article also ID variants in COMMD9 and CCDC93 to conclude that RSS is a recyclinopathy due to dysfunctional SNX17/Commander/WASH-mediated endosome recycling. Also as reported in DET1 submission, these proband were also homozygous for a variant in DET1 (c.76C>T, p.R26W). Sources: Literature |
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| Paediatric disorders - additional genes v6.14 | DET1 |
Sarah Leigh gene: DET1 was added gene: DET1 was added to Paediatric disorders - additional genes. Sources: Literature Mode of inheritance for gene: DET1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DET1 were set to 39937864 Phenotypes for gene: DET1 were set to neurological defects and lethality Review for gene: DET1 was set to RED Added comment: PMID: 39937864 reports a family where the three affected siblings were homozygous for a variant in DET1 (c.76C>T, p.R26W) and also for a variant in COMMD4 (c.122T>G; p.L41R). These genes are both on chromosome 15, separated by 13 Mb and are likely to co-segregate. The parents of these cases were healthy, heterozygous carriers of the DET1 p.R26W variant. The cases described developed lethal developmental abnormalities and the longest lived sib died at 8 months old. Extensive functional studies were reported in PMID: 39937864 and using Det1- deficient mice and human-induced pluripotent stem cells (iPSCs) expressing DET1R26W, the authors were able to show that DET1 is essential for normal neuronal development. Sources: Literature |
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