Deafness, Autosomal Recessive 93

A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-93 (DFNB93) is caused by homozygous mutation in the CABP2 gene (607314) on chromosome 11q13.

Description

Autosomal recessive deafness-93 is characterized by moderate to severe prelingual deafness and a distinctive U-shaped audiogram (Tabatabaiefar et al., 2011).

Clinical Features

Tabatabaiefar et al. (2011) studied a consanguineous Iranian family in which 4 sibs had stable bilateral symmetric prelingual moderate to severe deafness. Affected family members used a combination of sign language and oral communication. The hearing impairment was slightly more pronounced in the mid-frequencies, resulting in a distinctive shallow U-shaped audiogram. Tympanometry showed normal static compliance and normal middle ear pressures.

Schrauwen et al. (2012) examined affected individuals from 2 unrelated consanguineous Iranian families segregating autosomal recessive deafness. All affected individuals had prelingual stable bilateral hearing loss with similar audiometric profiles: the hearing loss was moderate to severe and was more pronounced in the mid-frequencies, resulting in a typical U-shaped audiogram. The affected individuals showed ectomorphic and marfanoid features; ophthalmologic examination was unremarkable except for 1 patient who had myopia and astigmatism, and cardiac examination was unremarkable.

Mapping

In a consanguineous Iranian family segregating autosomal recessive nonsyndromic deafness in which 14 DFNB loci among non-Caucasians had been ruled out, Tabatabaiefar et al. (2011) performed a genomewide linkage scan and found significant linkage on chromosome 11q12.3-q13.3 with a maximum multipoint lod score of 3.4 between SNPs rs1783811 and rs1671063. Analysis of additional markers and recombination events delineated a 9.62-Mb interval between markers D11S1765 and D11S1975, with a maximum multipoint lod score of 3.5 for the region between D11S1337 and D11S4136. Tabatabaiefar et al. (2011) noted that this deafness locus, designated DFNB93, was distinct from 5 other deafness loci that had previously been mapped to chromosome 11q.

Molecular Genetics

In a consanguineous Iranian family with deafness mapping to chromosome 11q12.3-q13.3, originally studied by Tabatabaiefar et al. (2011), Schrauwen et al. (2012) performed next-generation sequencing and identified a splice site mutation in the CABP2 gene (607314.0001) that was confirmed by Sanger sequencing and segregated with disease in the family. Sequencing the CABP2 gene in 2 other Iranian families segregating autosomal recessive deafness with a shallow U-shaped audiogram similar to that of the first family revealed homozygosity for the same splice site mutation in affected members; haplotype analysis suggested that the mutation arose on the same ancestral haplotype in all 3 Iranian families. Subsequent sequencing of the CABP2 gene in 24 Belgian and Dutch probands with moderate to severe hearing loss revealed no mutations, and no CABP2 mutations were found in 2 Usher syndrome (see 276900) families who had genotypes compatible with linkage to the DFNB93 locus.