The relationship between NDUFV1 and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of November 20, 2019. The NDUFV1 gene encodes the NADH:ubiquinone oxidoreductase (complex I) flavoprotein 1, a core subunit of mitochondrial complex I. Defects of this protein lead to complex I deficiency.
The NDUFV1 gene was first reported in relation to autosomal recessive Leigh syndrome spectrum in 2001 (PMID: 11349233). Evidence supporting this gene-disease relationship includes case-level data and experimental data.
This curation included nine unique variants identified in nine cases from seven publications (PMIDs: 23266820, 29976978, 11349233, 27344648, 30090137, 23334465, 21696386). No segregation data were available. Loss of function is implicated as the mechanism of disease. This gene-disease association is also supported by known protein interactions, animal models, and functional alterations in patient cells (PMIDs: 11349233, 30972103, 19672299, 27509854).
In summary, there is definitive evidence to support this gene-disease relationship, including that more than three years have elapsed from the first proposal of the association. This classification was approved by the NICHD U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel November 20, 2019 (SOP Version 7).
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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