DSE was first reported in relation to musculocontractural Ehlers-Danlos syndrome type 2 (mcEDS2) in 2013 (Muller et al., PMID:23704329). This protein coding gene maps to chromosome 6q22. The protein encoded by this gene is localized to the endoplasmic reticulum where it functions to convert D-glucuronic acid to L-iduronic acid residues during the biosynthesis of dermatan sulfate. To date, 9 specific variants have been reported in relation to 15 cases (Minatogawa et al., PMID:35842784, Yoshizawa et al., PMID:36833362). These mutations represent homozygous missense, frameshift, and nonsense mutations. Common symptoms among the reported cases include characteristic facial features, congenital contractures, joint hypermobility, skin manifestations, and muscle weakness. The gene-disease relationship is also supported by functional evidence including reduced DSE protein expression in patient-derived fibroblasts (Muller et al., PMID:23704329, Syx et al., PMID:25703627, Minatogawa et al., PMID:35842784) and lack of dermatan sulfate in patient urine samples (Latrup et al., PMID:32130795). Further evidence comes from skin composition and strength changes and altered protein expression observed in DSE-/- mice (Maccarana et al., PMID:19687302). In summary, there is definitive evidence supporting the relationship between DSE and mcEDS2. This has been repeatedly demonstrated in both research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date September 4, 2025 (SOP Version 11).
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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