NARS2 was first reported in relation to autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL) in 2015 (Simon 2015 PMID:25807530). Of note, this gene has also been associated with Leigh syndrome (Simon 2015), Alpers syndrome (Sofou 2015), and mitochondrial disorder (Vanlander 2015, Wang 2016) and Perrault syndrome in the family described in Simon et al. 2015 could not be ruled out. The split curation for autosomal recessive Leigh syndrome has been curated separately. Two missense variants that have been reported in one proband in one publication is included in this curation. Variants in this gene segregated with disease in 5 additional family members (PMID: 25807530). The mechanism of pathogenicity is unknown. This gene-disease association is also supported by expression studies in human and mouse cochlea. (PMID: 25807530). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was originally evaluated by the Hearing Loss GCEP on 12/19/2017. It was reevaluated on 11/17/2021using SOP v8. As a result of this reevaluation, the classification did not change as no new information was published.
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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