| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Osteopetrosis v0.38 | BORCS5 | Zornitza Stark Marked gene: BORCS5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteopetrosis v0.38 | BORCS5 | Zornitza Stark Gene: borcs5 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteopetrosis v0.38 | BORCS5 | Zornitza Stark Publications for gene: BORCS5 were set to 40621786; 7577667 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteopetrosis v0.37 | BORCS5 | Zornitza Stark edited their review of gene: BORCS5: Changed publications: 40621786, 7577667, 40385417 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteopetrosis v0.37 | BORCS5 |
Zornitza Stark gene: BORCS5 was added gene: BORCS5 was added to Osteopetrosis. Sources: Literature Mode of inheritance for gene: BORCS5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BORCS5 were set to 40621786; 7577667 Phenotypes for gene: BORCS5 were set to Neuroaxonal dystrophy (NAD) with osteopetrosis syndrome (OMIM # 600329) Review for gene: BORCS5 was set to RED Added comment: Disease entity originally described in 1995 but genetic basis unknown. Report of consanguineous family with two affected fetuses, homozygous for same missense variant, p. Arg301His. However, note preprint PMID 40385417, describing 12 individuals from 7 families with a spectrum of abnormalities (osteopetrosis not mentioned), suggestive of lysosomal disorder. homozygous loss-of-function variants presented with prenatally lethal arthrogryposis multiplex congenita, brain malformations, and neuropathological evidence of diffuse neuroaxonal dystrophy. Individuals with missense variants presented differently, with microcephaly, developmental epileptic encephalopathy, intellectual disability, optic atrophy, spasticity, and progressive movement disorders. In this group, brain MRI showed diffuse hypomyelination and progressive global cerebral atrophy, consistent with neurodegeneration. Borcs5 knockout in zebrafish exhibited microcephaly, motor deficits, and seizures, mirroring the patients' clinical presentation. At the cellular level, BORCS5 loss-of-function but not missense variants, resulted in lower protein expression and impaired BORC assembly, paralleled by perinuclear lysosomal clustering. However, both loss-of-function and missense BORCS5 variants were associated with reduced total lysosomal proteolysis, reduced activity of the lysosomal hydrolases glucocerebrosidase and cathepsin B, and presence of multilamellar bodies, indicating lysosomal dysfunction. Sources: Literature |
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