The relationship between SDHAF1 and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of January 13, 2020. The SDHAF1 gene encodes succinate dehydrogenase (complex II) assembly factor 1.
The SDHAF1 gene was first reported in relation to autosomal recessive Leigh syndrome spectrum in 2009 (PMID: 19465911). Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. This curation included one homozygous variant identified in one case in one publication (PMID: 19465911). Segregation data includes 4 affected individuals and 12 unaffected individuals in one kindred (PMID: 19465911). Loss of function is implicated as the mechanism of disease. This gene-disease association is also supported by functional alteration in patient cells (PMIDs: 19465911, 22995659).
In summary, there is limited 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 on January 13, 2020 (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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