Submission Details

Pathogenic variants in the SLC35A2 gene have been reported in the literature in several individuals with features of a congenital disorder of glycosylation (CDG), usually characterized by refractory epileptic encephalopathy, hypsarrhythmia, intellectual disability, hypotonia, dysmorphic features and skeletal abnormalities. The presentation of individuals with pathogenic variants is variable and may also include feeding difficulties/failure to thrive, microcephaly, ocular abnormalities, as well as cardiac, hepatic, and renal abnormalities. Of note, carbohydrate deficient transferrin analysis (a common tool to screen for CDGs) has been reported to be of limited use in the diagnosis of this disorder. Loss of function and missense variants have been reported in association with disease. As this gene is on the X chromosome, affected individuals are primarily female, but males with this condition have also been reported (PMID:23561849, PMID:30194038, PMID:30817854). Of note, variants in the somatic setting have also been identified in individuals with this condition (PMID:29679388). Evidence supporting this gene disease pair includes experimental data as well. Supporting experimental data has demonstrated that loss of this gene severely impairs the transport of UDP galactose into the Golgi which results in the synthesis of truncated glycans lacking galactose (PMID:3141404, PMID:23561849, PMID:30817854). SLC35A2 is definitively associated with X-linked complex neurodevelopmental disorder. This has been demonstrated in both the clinical and research settings and this evidence has been maintained over time.