Variants in ST3GAL3 were first reported in a family with autosomal recessive complex neurodevelopmental disorder in 2011 (PMID: 21907012). Including the initial report, a total of four unique homozygous ST3GAL3 variants (three missense variants and one nonsense variant) in four families have been reported (PMID: 21907012, 23252400, 31584066). Clinical features observed in affected individuals include developmental delay, nonsyndromic intellectual disability, and epileptic encephalopathy (in two families). In one family, the ST3GAL3 variant segregated with disease in three additional family members (PMID: 23252400). ST3GAL3 encodes a sialyltransferase. Diminished enzyme activity and/or altered subcellular localization of the mutant protein were demonstrated by functional studies, supporting a loss-of-function disease mechanism (PMID: 21907012, 23252400, 31584066). This gene-disease relationship is further supported by functional alteration in patient cells, mouse models, and expression studies (PMID: 8027041, 22735313, 25846372, 30089820). In summary, there is moderate evidence to support this gene-disease association. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 6/3/2020.
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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