The relationship between SDHA and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of May 8, 2019. 14 articles were reviewed. SDHA was first reported in relation to autosomal recessive Leigh syndrome spectrum in 1995 (Bourgeron et al., PMID 7550341). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 7 probands in 6 publications (PMIDs 7550341, 10746566, 16361598, 16798039, 22972948, 24781757). This gene-disease association is supported by the known protein interactions, model systems, and rescue. The mechanism for disease is complex II deficiency. In summary, there is moderate evidence to support the relationship between SDHA and autosomal recessive Leigh syndrome spectrum. This classification was approved by the NICHD U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on May 13, 2019 (SOP Version 6).
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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