DEAFNESS, AUTOSOMAL RECESSIVE 104; DFNB104

Diaz-Horta et al. (2014) reported a consanguineous Turkish family in which 6 individuals had congenital profound nonsyndromic sensorineural hearing loss. Available audiograms did not suggest progression of the hearing loss. Evoked otoacoustic emissions, acoustic reflexes, and auditory brainstem responses were absent in affected individuals. None had balance problems.

▼ Inheritance
The transmission pattern of DFNB104 in the family reported by Diaz-Horta et al. (2014) was consistent with autosomal recessive inheritance.

▼ Molecular Genetics
In 6 affected members of a consanguineous Turkish family with DFNB104, Diaz-Horta et al. (2014) identified a homozygous splice site mutation in the FAM65B gene (611410.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. In vitro functional expression studies showed that the mutant protein accumulated abnormally in cytoplasmic inclusion bodies and did not reach the membrane. Mutations in the FAM65B gene were not found in 248 other families with autosomal recessive deafness or in 437 simplex cases with deafness. Diaz-Horta et al. (2014) concluded that FAM65B is a plasma membrane-associated protein of hair cell stereocilia that is essential for hearing.

▼ Animal Model
Diaz-Horta et al. (2014) found that fam65b was expressed in the otic vesicle of zebrafish. Morpholino knockdown of the fam65b gene in zebrafish embryos resulted in a significant reduction in the number of saccular hair cells and neuromasts, and caused hearing loss.