Deafness, Autosomal Dominant 74

A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-74 (DFNA74) is caused by heterozygous mutation in the PDE1C gene (602987) on chromosome 7p14. One such family has been reported.

Description

Autosomal dominant deafness-74 (DFNA74) is characterized by nonsyndromic postlingual progressive hearing loss, with onset in the third decade of life in most affected individuals (Wang et al., 2018).

Clinical Features

Wang et al. (2018) reported a large Chinese family in which 28 members over 5 generations had nonsyndromic bilateral symmetric hearing loss. Onset was in the third decade of life in most affected individuals, with the earliest onset detected at age 14 years in a fifth-generation individual. Deafness showed gradual progression from mild to profound, involving the high frequencies in most patients.

Molecular Genetics

In a large Chinese family segregating autosomal dominant nonsyndromic postlingual progressive deafness over 5 generations, in which the common Chinese deafness variants as well as mutation in 180 known deafness-associated genes had been excluded, Wang et al. (2018) performed whole-exome sequencing and identified a heterozygous missense mutation in the PDE1C gene (A320S; 602987.0001) that segregated fully with disease in the family and was not found in 215 ethnically matched controls. The variant was present at low frequencies in the ExAC and gnomAD databases in East Asians only (global minor allele frequency of approximately 0.00005).