SNX10 was first reported in relation to autosomal recessive osteopetrosis 8 in 2012 (Aker et al., PMID: 22499339). Osteopetrosis is a metabolic bone disease characterized by increased bone density due to impaired bone resorption. The autosomal recessive form manifests in the first months of life with characteristic facial appearance, choanal stenosis, compression of cranial nerves (leading frequently to blindness, rarely to deafness and facial palsy), bone marrow insufficiency, hepatosplenomegaly, dental anomalies, and hypocalcaemia. Eighteen unique variants (missense, nonsense, frameshift, splice-site, and gross deletions) that have been reported in 24 probands in 11 publications (PMIDs: 22499339, 23123320, 23280965, 27391121, 27187610, 29090071, 29620724, 30977576, 33678645, 36526684, 36703223) are included in this curation. The maximum score for genetic evidence has been reached (12 pts). All except one proband had a homozygous variant in the SNX10 gene. This gene-disease relationship is supported by biochemical function study, expression data, functional alteration data, and two mouse models (PMIDs: 22174188, 25212774, 28592808, 25811986, 32278070). In summary, there is definitive evidence to support the relationship between SNX10 and autosomal recessive osteopetrosis 8. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Skeletal Disorders GCEP on the meeting date June 24, 2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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