GRHL2 was first associated with autosomal dominant non-syndromic hearing loss as early as 2002 (Peters et al., PMID: 12393799). At least 7 unique variants (frameshift, splice site, exon deletion) have been reported in humans. This association was made using case-level data, animal models, expression studies, and protein interaction studies. Association is seen in at least 8 probands in 5 publications and 2 ClinVar SCVs (PMIDs: 12393799, 23813623, 25342930, 27911912, 32048449, SCV000575569.4, SCV000344371.3). Variants in this gene segregated with disease in 16 additional family members (PMIDs: 12393799, 23813623, 32048449). The mechanism for disease is haploinsufficiency (PMID: 12393799, 23813623, 25342930). This gene-disease association is supported by a zebrafish transposon-mediated gene trap model and mRNA rescue, expression studies in the inner ear of mice, and protein interaction studies showing GRHL2's interaction with claudins. In summary, GRHL2 is definitively associated with autosomal dominant non-syndromic hearing loss.
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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