Deafness, Autosomal Recessive 91

A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-91 (DFNB91) is caused by homozygous mutation in the SERPINB6 gene (173321) on chromosome 6p25. One such family has been reported.

Clinical Features

Sirmaci et al. (2010) reported a consanguineous Turkish family with nonsyndromic progressive hearing loss. Although the precise age of onset could not be ascertained, the youngest affected individual, who was 23 years old, reported loss of hearing after age 20. The hearing loss was progressive and age-dependent, consistent with a loss of function of an intracellular protease inhibitor. There were no other features, and vestibular function was normal.

Molecular Genetics

By genomewide linkage analysis followed by candidate gene sequencing in affected members of a consanguineous Turkish family with nonsyndromic progressive hearing loss, Sirmaci et al. (2010) identified a homozygous truncating mutation in the SERPINB6 gene (E245X; 173321.0001), resulting in a loss of function. Mutation in the SERPINB6 gene was not found in 542 Turkish, Greek, American, and Palestinian families mostly with congenital hearing loss, suggesting that SERPINB6 mutations are not a common cause of early hearing loss. Sirmaci et al. (2010) demonstrated that in mouse embryos Serpinb6 is expressed in the inner ear during development. Sirmaci et al. (2010) concluded that SERPINB6 plays an important role in the inner ear in the protection against leakage of lysosomal content during stress, and that loss of this protection results in cell death and sensorineural hearing loss.

Shearer et al. (2014) stated that they had identified a partial deletion in the SERPINB6 gene as a cause of autosomal recessive nonsyndromic hearing loss (their table 1), but provided no additional information.