Deafness, Autosomal Dominant 56

A number sign (#) is used with this entry because autosomal dominant deafness-56 (DFNA56) is caused by heterozygous mutation in the TNC gene (187380) on chromosome 9q33.

Description

Autosomal dominant deafness-56 is a form of nonsyndromic sensorineural hearing loss. Hearing impairment shows postlingual onset and is progressive (summary by Zhao et al., 2013).

Clinical Features

Zhao et al. (2013) reported a large 5-generation Chinese family with postlingual, bilateral, symmetric nonsyndromic sensorineural hearing loss. The age at onset ranged from 8 to 30 years. The hearing loss first manifest as mild in low frequencies and progressed to involve all frequencies with age. There were no vestibular signs, and imaging did not show any abnormalities of the middle or inner ear structures. Five members of an unrelated Chinese family had late-onset progressive hearing loss initially affecting high frequencies.

Inheritance

The transmission pattern of nonsyndromic sensorineural hearing loss in the 5-generation Chinese family reported by Zhao et al. (2013) was consistent with autosomal dominant inheritance.

Mapping

By genomewide linkage analysis of a large 5-generation Chinese family with autosomal dominant hearing loss, Zhao et al. (2013) found linkage to a 28.54-Mb region on chromosome 9q31.3-q34.3 (maximum 2-point lod score of 4.57 at D9S177). The locus was designated DFNA56.

Molecular Genetics

In affected members of a large Chinese family with autosomal dominant hearing loss, Zhao et al. (2013) identified a heterozygous mutation in the TNC gene (V1773M; 187380.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In affected members of an unrelated Chinese family with postlingual onset of autosomal dominant hearing loss, Zhao et al. (2013) identified a different heterozygous mutation in the TNC gene (T1796S; 187380.0002). Functional studies of the variants were not performed. Zhao et al. (2013) stated that TNC is present in the basilar membrane and the osseous spiral lamina of the cochlea; it plays a role in cochlear development and sensory receptor recovery after ototoxic injury in birds. Zhao et al. (2013) suggested that mutation in the TNC gene would interrupt its interaction with other proteins and receptors, resulting in a loss of repair mechanisms.