The relationship between SQOR and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of November 23, 2020. The SQOR gene encodes sulfide quinone oxidoreductase, an enzyme that breaks down hydrogen sulfide which, when accumulated, inhibits complex IV.
The SQOR gene was first reported in relation to autosomal recessive Leigh syndrome spectrum in 2020 (PMID: 32160317). Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included two variants identified in two cases from one publication (PMID: 32160317). Of note, there was much debate among this Expert Panel if Subject II-3 from Family B should be scored as the variant was also found to be homozygous in two healthy siblings. However, after extensive discussion within the Expert Panel, it was decided to score this case but downgrade the score. No segregation data were available. Loss of function is implicated as the mechanism of disease. This gene-disease association is also supported by biochemical function and expression (PMIDs: 27977873, 22067608).
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 November 23, 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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