Deafness, Autosomal Recessive 102

A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-102 (DFNB102) is caused by homozygous mutation in the EPS8 gene (600206) on chromosome 12p12. One such family has been reported.

Clinical Features

Behlouli et al. (2014) reported 2 sibs, born of consanguineous Algerian parents, with isolated and profound congenital deafness affecting all frequencies. Auditory brainstem responses to stimuli were not detected. Neither patient had evidence of a vestibular defect.

Mapping

DFNB102 was mapped to chromosome 12p12 by the identification of mutations in the EPS8 gene in affected members of an Algerian family by Behlouli et al. (2014). Another form of autosomal recessive deafness, DFNB62 (610143), had been mapped within the same region.

Molecular Genetics

In 2 sibs, born of consanguineous Algerian parents, with autosomal congenital deafness, Behlouli et al. (2014) identified a homozygous truncating mutation in the EPS8 gene (Q30X; 600206.0001). The mutation was found by whole-exome sequencing. Behlouli et al. (2014) noted that the EPS8 gene is expressed in the hair bundle, the sensory antenna of the auditory sensory cells of the cochlea that operate mechanoelectrical transduction necessary for hearing, and that Eps8-null mice are profoundly deaf, with abnormally short hair bundle stereocilia (see ANIMAL MODEL).

Animal Model

Manor et al. (2011) found that knockout of Eps8 in mice reduced the length of stereocilia in cochlear hair cells and caused profound deafness.

Independently, Zampini et al. (2011) found that Eps8 was required for normal stereocilia elongation and that knockout of Eps8 in mice resulted in deafness. Eps8 knockout mice showed increased rows of stereocilia and reduced length of predominantly tall stereocilia in both inner and outer hair cells. Eps8 -/- inner hair cells failed to develop adult-type ion channels, but Eps8 -/- outer hair cells developed normally.