Deafness, Autosomal Recessive 107

A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-107 (DFNB107) is caused by compound heterozygous mutation in the WBP2 gene (606962) on chromosome 17q25.

Clinical Features

Buniello et al. (2016) identified 2 Chinese probands with DFNB107: a 5-year-old boy with bilateral prelingual deafness, and a 9-year-old girl with severe to profound bilateral hearing loss. The children were identified from a screening of 8,087 probands with deafness in China.

Molecular Genetics

Using targeted next-generation sequencing to screen 8,087 probands with deafness and 1,823 unaffected controls in China, Buniello et al. (2016) identified 2 probands with compound heterozygous missense mutations in the WBP2 gene (606962.0001-606062.0003). The parents in each family were heterozygous for one of the mutations.

Animal Model

Buniello et al. (2016) performed a high-throughput screen for hearing impairment using auditory brainstem responses (ABR) in Wbp2-deficient mice. At P14, ABR thresholds were comparable to those in littermate controls. Loss of sensitivity to frequencies of 24 kHz and above was apparent by 4 weeks, and became more evident at 14 and 28 weeks, spreading to lower frequencies by 44 weeks. Buniello et al. (2016) demonstrated that the hearing loss was associated with reduced expression of Esr1, Esr2 (601663), and Pgr in the cochlea and disruption of expression of key postsynaptic proteins. Wbp2 mutants were fertile and showed no other abnormalities.