SPTLC2 was first reported in relation to autosomal dominant hereditary sensory and autonomic neuropathy type 1 (HSAN1) in 2010 (Rotthier A, et al., 2010, PMID: 20920666). HSAN1 is an axonal peripheral neuropathy associated with progressive distal sensory loss and severe ulcerations with variable age of onset from first to sixth decade of life. SPTLC2 encodes a subunit of the enzyme serine palmitoyltransferase (SPT) which catalyzes the first and rate-limiting step in the de novo sphingolipid synthesis pathway. The mechanism of pathogenicity is known to be partial or complete loss of function which leads to the accumulation of the atypical and neurotoxic sphingoid metabolite 1-deoxy-sphinganine. This gene-disease association is also supported by experimental evidence, including animal models, expression studies, and functional assays (PMIDs: 26573920; 20920666; 29761896; 16216550; 25567748). At least 7 missense variants in 9 families have been reported in humans and are included in this curation (PMIDs: 20920666; 23658386; 26573920; 30955194). Evidence supporting this gene-disease relationship includes case level data. In summary, SPTLC2 is definitively associated with autosomal dominant hereditary sensory and autonomic neuropathy type 1 (HSAN1). This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
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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