DMGDH was first reported in relation to autosomal recessive dimethylglycine dehydrogenase deficiency in 1999 (Moolenaar et al., PMID:10102904) with the variant being identified in 2001 (Binzak et al; PMID: 11231903). Only this one homozygous missense variant with functional evidence to support pathogenicity has been reported in humans, with the phenotypes consisting of a distinctive fish-like odor, increased serum CK, muscle fatigue, and increased levels of N,N-dimethylglycine in urine. Evidence supporting this gene-disease relationship includes only this case-level data and biochemical function data which implicates the DMGDH mutant's decrease in choline metabolism as potentially causal for these phenotypes. In summary, there is limited evidence to support this gene-disease relationship, particularly due to the lack of reported variants in humans. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.This classification was approved by the ClinGen Aminoacidopathy Working Group on 06/28/19 (SOP Version 6). It was reevaluated on 10/14/2022 with no new evidence found. As a result of this reevaluation, the classification remains Limited.
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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