Confirmation of GRHL2 as the gene for the DFNA28 locus

Abstract

More than 10 years ago, a c.1609_1610insC mutation in the grainyhead-like 2 (GRHL2) gene was identified in a large family with nonsyndromic sensorineural hearing loss, so far presenting the only evidence for GRHL2 being an autosomal-dominant deafness gene (DFNA28). Here, we report on a second large family, in which post-lingual hearing loss with a highly variable age of onset and progression segregated with a heterozygous non-classical splice site mutation in GRHL2. The c.1258-1G>A mutation disrupts the acceptor recognition sequence of intron 9, creating a new AG splice site, which is shifted by only one nucleotide in the 3′ direction. cDNA analysis confirmed a p.Gly420Glufs*111 frameshift mutation in exon 10. © 2013 Wiley Periodicals, Inc.