CCDC115 was first reported in relation to autosomal recessive developmental and epileptic encephalopathy in 2016 (Jansen et al., PMID 26833332). Seven variants (missense, nonsense, large deletion) that have been reported in 10 probands in 4 publications (PMIDs 26833332, 29759592, 32043565, 33413482) are included in this curation. Patients have a range of symptoms, including hepatosplenomegaly, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. The disease mechanism appears to be biallelic loss of function. Heterozygous carriers are reportedly unaffected. This gene-disease relationship is also supported by the in vitro assays showing a deficiency in Golgi glycosylation and hyperlipidemia (PMIDs 26833332, 34626841) as well as expression in relevant tissues (PMID 16378758). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on September 4th, 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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