Deafness, Autosomal Recessive 22

A number sign (#) is used with this entry because autosomal recessive deafness-22 (DFNB22) is caused by homozygous mutation in the gene encoding otoancorin (OTOA; 607038) on chromosome 16p12.

Clinical Features

Zwaenepoel et al. (2002) reported a consanguineous Palestinian family with autosomal recessive moderate to severe prelingual sensorineural deafness.

Lee et al. (2013) reported 3 consanguineous Pakistani families with prelingual onset of severe to profound sensorineural hearing loss affecting all frequencies.

Inheritance

The transmission pattern of deafness in the families reported by Lee et al. (2013) was consistent with autosomal recessive inheritance.

Mapping

Zwaenepoel et al. (2002) searched a collection of 200 large affected families with deafness to determine whether the deafness locus in any mapped to chromosome 16p12.2, where the OTOA gene is localized. OTOA is an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, and was considered by the authors to be a candidate gene. One consanguineous Palestinian family was shown to segregate with a locus, termed DFNB22, on chromosome 16p13.1-q11.2.

Molecular Genetics

In a consanguineous Palestinian family with prelingual sensorineural recessive deafness mapping to chromosome 16p13.1-q11.2, Zwaenepoel et al. (2002) identified a homozygous splice site mutation in the OTOA gene (IVS12+2T-C; 607038.0001).

In affected sibs from a consanguineous Palestinian family with autosomal recessive prelingual deafness, Shahin et al. (2010) identified a homozygous 500-kb deletion that resulted in complete deletion of the OTOA gene (607038.0002). The deletion was flanked by segmental duplications at chromosome 16q, suggesting nonallelic homologous recombination as the mechanism. The deletion was observed in the heterozygous state in 3 (1.0%) of 288 unrelated Palestinian controls.

In affected members of 3 consanguineous Pakistani families with DFNB22, Lee et al. (2013) identified 2 different homozygous missense mutations in the OTOA gene (G451D, 607038.0003 and P627S, 608038.0004). Functional studies of the variants were not performed, but both mutations were predicted to interrupt the superhelical structure of OTOA, which would result in an inability of otoancorin to stabilize the tectorial members on top of sensory hair cells in the inner ear.