Deafness, Autosomal Dominant 44

A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-44 (DFNA44) is caused by heterozygous mutation in the CCDC50 gene (611051) on chromosome 3q28. One such family has been reported.

Clinical Features

Modamio-Hoybjor et al. (2003) reported a 5-generation Spanish family in which 18 members had onset of moderate hearing loss, mainly affecting low-mid frequencies, between 6 and 10 years of age. Deafness later involved all frequencies and progressed to profound hearing loss in the sixth decade.

Mapping

By linkage analysis, Modamio-Hoybjor et al. (2003) identified a novel DFNA locus on chromosome 3q28-q29 in a Spanish family with postlingual and progressive hearing loss. They narrowed the locus, DNFA44, to a 3-cM interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of 2 genes in this interval, claudin-16 (603959) and fibroblast growth factor-12 (601513), revealed no disease-causing mutations.

Molecular Genetics

Modamio-Hoybjor et al. (2007) identified the CCDC50 gene within the critical linkage area and considered it a candidate gene for DFNA44 hearing loss, given that it is expressed in cochlea. Sequence analysis of all exons and flanking intronic sequences of CCDC50 in an affected subject revealed a heterozygous mutation in exon 11 (1394_1401dupCACGGCAT; 611051.0001). CCDC50 encodes Ymer, an effector of epidermal growth factor (EGF)-mediated cell signaling that is ubiquitously expressed in different organs and has been suggested to inhibit downregulation of an EGF receptor. Modamio-Hoybjor et al. (2007) suggested that DFNA44 hearing loss may result from a time-dependent disorganization of the microtubule-based cytoskeleton in the pillar cells and stria vascularis of the adult auditory system.