Deafness, Autosomal Recessive 99

A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-99 (DFNB99) is caused by homozygous mutation in the TMEM132E gene (616178) on chromosome 17q12. One such family has been reported.

Clinical Features

Cheng et al. (2003) and Li et al. (2015) reported 2 brothers, born of consanguineous Chinese parents, with prelingual, bilateral, severe-to-profound sensorineural hearing loss. There was no evidence of vestibular dysfunction.

Inheritance

The transmission pattern of DFNB99 in the family reported by Cheng et al. (2003) was consistent with autosomal recessive inheritance.

Mapping

By homozygosity mapping in a consanguineous Chinese family with autosomal recessive hearing loss, Cheng et al. (2003) identified a 5.07-cM candidate region between markers D17S1850 and D17S1818 on chromosome 17q12.

Molecular Genetics

In 2 brothers, born of consanguineous Chinese parents, with DFNB99, Li et al. (2015) identified a homozygous missense mutation in the TMEM132E gene (R420Q; 616178.0001). The mutation, which was found by a combination of linkage analysis (Cheng et al., 2003) and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in 500 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. Sequencing of the TMEM132E gene in 95 additional Chinese probands with autosomal recessive hearing loss did not identify any additional pathogenic mutations.

Animal Model

Li et al. (2015) found high expression of the Tmem132e gene in murine inner hair cells in the organ of Corti. Morpholino-mediated knockdown of tmem132e in zebrafish delayed sound-induced startle response and caused circular swimming behavior. Tmem132e morphants showed significantly reduced extracellular receptor potentials and impaired mechanoelectrical transduction in hair cells of inner ear relative to controls. Scanning electron microscopy revealed disorganized lateral line neuromasts in tmem132e morphants. Coinjection of wildtype human TMEM132E with the tmem132e morpholino rescued the phenotype.