The relationship between TACO1 and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of August 21, 2019. The TACO1 gene encodes the translational activator of cytochrome c oxidase I protein, which is required for translation of the cytochrome c oxidase subunit I, a component of complex IV of the mitochondrial respiratory complex. The TACO1 gene was first reported in relation to autosomal recessive Leigh syndrome spectrum in 2009 (PMID: 19503089). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Two loss of function variants in this gene have been reported in two consanguineous families in two publications (PMIDs: 19503089, 25044680). Variants in this gene segregated with disease in five additional family members, and segregation evidence was scored for one family (PMID: 19503089). Loss of function is implicated as the mechanism of disease. This gene-disease relationship is also supported by the biochemical function of the protein, functional alteration and rescue experiments in patient fibroblasts, and a homozygous knockout mouse model showed complex IV deficiency and a similar phenotype to human patients (PMIDs: 19503089, 27319982). In summary, there is moderate evidence to support the relationship between TACO1 and Leigh syndrome spectrum. This classification was approved by the NICHD U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on August 21, 2019.
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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