CRYM was first reported in relation to autosomal dominant nonsyndromic hearing loss in 2003 (Abe et al., PMID: 12471561). Three variants (stop loss, missense) that have been reported in three probands in two publications are included in this curation. These variants segregated with disease in 7 additional family members in two families (PMIDs: 12471561, 32742378). The mechanism of pathogenicity is unknown. This gene-disease association is also supported by expression studies and in vitro functional assays (PMIDs: 16740909, 18448257, 24676347, 26915689). Of note, both homozygous and heterozygous CRYM null mice do not have hearing loss (PMID: 17264173). 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 2/16/2017. It was reevaluated on 9/21/2021 (SOP v8). As a result of this reevaluation, the classification did not change. Although new literature was published (PMID: 32742378), the scoring still corresponded to a limited gene-disease relationship.
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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