Deafness, Autosomal Dominant 68

A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-68 (DFNA68) is caused by heterozygous mutation in the HOMER2 gene (604799) on chromosome 15q25. One such family has been reported.

Clinical Features

Azaiez et al. (2015) studied a multigenerational kindred of European descent segregating autosomal dominant deafness. Pure tone audiometric evaluation of affected individuals revealed postlingual progressive bilateral hearing loss; bone conduction thresholds excluded conductive hearing impairment. Onset of hearing loss typically occurred in the first decade of life and involved the high frequencies; there was significant subsequent progression of hearing loss over all frequencies, with an annual threshold deterioration of 1.2 to 1.6 dB per year. No syndromic features or autoimmune phenotypes were found on clinical examination.

Molecular Genetics

In a multigenerational kindred segregating autosomal dominant postlingual progressive sensorineural hearing loss, in which plausible pathogenic variants in known deafness-associated genes had been excluded, Azaiez et al. (2015) performed whole-exome sequencing and identified a heterozygous missense mutation in the HOMER2 gene (R185P; 604799.0001) that segregated with disease.