SERPINB6 was first reported in relation to autosomal recessive nonsyndromic hearing loss in 2010 (Sirmaci et al., PMID: 20451170). Four variants (missense, nonsense, frameshift, and canonical splice site) that have been reported in two probands in two publications (PMIDs: 20451170, 25719458, 33997018) are included in this curation. Variants in SERPINB6 were shown to segregate with disease as well. The mechanism of pathogenicity is known to be LOF. This gene-disease relationship is also supported by expression in the developing inner ear, altered expression in patients, functional alteration in patients, and a mouse model phenocopying disease (PMIDs: 20451170, 23669344). In summary, SERPINB6 is definitively associated with autosomal recessive nonsyndromic hearing loss. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This gene-disease pair was originally evaluated by the Hearing Loss GCEP on 10/5/2017 and reviewed again on 4/24/2018. It was reevaluated on 10/19/2022. As a result of this reevaluation, the classification did not change from moderate (SOP Version 9).
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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