The relationship between NDUFS8 and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of November 20, 2019. The NDUFS8 gene encodes the NADH:ubiquinone oxidoreductase (complex I) core subunit S8. Defects of this protein lead to complex I deficiency.
The NDUFS8 gene was first reported in relation to autosomal recessive Leigh syndrome spectrum in 1998 (PMID: 9837812). Evidence supporting this gene-disease relationship includes case-level data and experimental data.
This curation included seven unique variants identified in five cases from five publications (PMIDs: 9837812, 22200994, 15159508, 23430795, 20818383). 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 and animal models (PMIDs: 21924235, 19672299, 29285794, 27509854).
In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. 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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