CSGALNACT1 was first reported in relation to autosomal recessive mild skeletal dysplasia with joint laxity and advanced bone age (SDJLABA) in 2017 (Vodopiutz et al., PMID:27599773). CSGALNACT1 is a highly conserved gene mapped to chromosome 8p21. It encodes chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGalNAct-1) and plays a major role in the chondroitin sulfate chain biosynthesis and therefore in the synthesis of glycosaminoglycans. Persons with this condition typically present with mild skeletal dysplasia, advanced bone age, non-proportional short stature, hyperlordosis, pes planus, and joint laxity (PMIDs: 27599773, PMID:31325655, 31705726). Six variants (including missense, frameshift, and intragenic deletions) reported in 4 probands in 3 publications are included in this curation [PMIDs: 27599773, 31325655, 31705726]. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is supported by functional evidence, including significantly reduced CSGalNAct-1 activity in vitro (PMIDs: 27599773, 31705726). Further evidence comes from the observed skeletal dysplasia reminiscent of CSGALNACT1-/- mice (Watanabe et al., PMIDs:20812917, 31705726). The most recent report suggests the term CSGALNACT1-CDG (PMID: 31705726). 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 the meeting date June 5, 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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