DPAGT1 was first reported in relation to autosomal recessive congenital disorder of glycosylation in 2003 (Wu, et al., PMID: 12872255), and autosomal recessive congenital myasthenic syndrome in 2012 (Belaya, et al., PMID: 22742743). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism(s), inheritance pattern, or phenotypic variability. Therefore, both disease entities have been lumped into one disease entity. 27 variants (missense, in-frame indel, nonsense, frameshift, and splice) that have been reported in 16 probands in 6 publications (PMIDs: 22742743, 30117111, 22492991, 29356258, 24759841, 28662078) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by a mouse model and a biochemical function assay (PMIDs: 32714760, 10536042). In summary, there is definitive evidence supporting the relationship between DPAGT1 and autosomal recessive congenital disorder of glycosylation. This has been repeatedly demonstrated in both the 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 June 5, 2024 (SOP Version 10).
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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