DPM2 was first reported in relation to autosomal recessive congenital muscular dystrophy with intellectual disability and severe epilepsy (also known as congenital disorder of glycosylation, type Iu) in 2012 (Barone et al, PMID: 23109149). 5 variants (splice site, missense, nonsense) that have been reported in 4 probands are included in this curation. Patients have a range of symptoms, including acquired microcephaly, facial dysmorphism, respiratory distress, congenital contractures, scoliosis, hypotonia, and lack of psychomotor development. The disease mechanism is thought to be biallelic loss of function. Heterozygous carriers are unaffected. This gene-disease relationship is supported by DPM2's interaction with DPM1 and DPM3, the other members of the DPM synthase complex, as well as an animal model (PMID: 27291147). Co-transfection and immunoprecipitation experiments suggest that DPM2 is the regulatory subunit of this complex (PMIDs: 9724629, 10835346). 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 March 20, 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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