Deafness, Autosomal Recessive 16

A number sign (#) is used with this entry because of evidence that autosomal recessive deafness-16 (DFNB16) is caused by homozygous or compound heterozygous mutation in the STRC gene (606440) on chromosome 15q15.

Clinical Features

Villamar et al. (1999) reported a family with bilateral sensorineural hearing loss. Onset of hearing loss occurred in early childhood and was nonprogressive (ages of deaf individuals ranged from 35-60 years, and there were records of audiometric tests performed during childhood). The hearing impairment, which involved all frequencies, was moderate in the range of 125-1,000 Hz but severe in higher frequencies. Vestibular function was normal, and there were no symptoms of tinnitus. The phenotype could not be compared with those of the other families linked to the DFNB16 locus because clinical data had not been reported by Campbell et al. (1997).

Vona et al. (2015) reported 4 unrelated children with autosomal recessive nonsyndromic sensorineural deafness who had onset of symptoms between birth and 6 years of age. The patients had mild to moderate hearing loss with sloping high-frequency audiometric profiles.

Mapping

Campbell et al. (1997) mapped a recessive deafness locus, DFNB16, to 15q21-q22 by linkage studies of 3 consanguineous families from Pakistan, Palestine, and Syria. No clinical data on the families were provided. Analysis of recombinant haplotypes indicated that the locus was in the 20-cM interval delimited by markers D15S994 and D15S155. Acting on the results of homozygosity data, Campbell et al. (1997) narrowed the location of DFNB16 to the 15-cM distal part of the interval, between markers D15S1039 and D15S155. Villamar et al. (1999) narrowed the assignment of DFNB16 to the proximal 5-cM part of the interval, between D15S1044 and D15S132 (15q13-q21).

Molecular Genetics

Verpy et al. (2001) identified mutations in a protein called stereocilin, encoded by the STRC gene (606440). Using a candidate deafness gene approach, they reported a transcript that is expressed almost exclusively in the inner ear. Genomic analysis showed that STRC is located on chromosome 15q15. It contains 29 exons encompassing approximately 19 kb. STRC is tandemly duplicated, with the coding sequence of the second copy interrupted by a stop codon in exon 20. In 2 families affected by autosomal recessive nonsyndromal sensorineural deafness linked to the DFNB16 locus on 15q, Verpy et al. (2001) found 2 frameshift mutations and a large deletion in the copy of the gene containing 29 coding exons.

In one of the consanguineous deaf families linked to 15q22 reported by Campbell et al. (1997), Verpy et al. (2001) failed to find a mutation in the STRC gene. The deafness in these families was of a prelingual profound type and may be due to mutation in a second deafness gene in the 15q21.1 region.

Francey et al. (2012) used 3 different genotyping array platforms as well as Sanger sequencing to analyze 659 GJB2 (121011) mutation-negative pediatric probands with sensorineural hearing loss. Using both array genotyping information and sequencing data, the authors identified 17 STRC deletions, including 7 homozygous and 9 heterozygous deletions; by sequencing data alone, they identified 1 heterozygous deletion. After sequencing for point mutations, they found that 6 of 9 probands with a heterozygous deletion carried a novel variant in the STRC gene; 4 of the variants were confirmed by parental analysis to be on the trans allele. All patients with biallelic STRC alterations had mild to moderate hearing loss. The findings suggested that STRC may be a common contributor to nonsyndromic sensorineural hearing loss. Functional studies of the deletions and variants were not performed.

In 4 unrelated children with DFNB16, Vona et al. (2015) identified biallelic alterations in the STRC gene. Three patients were compound heterozygous for a gene deletion and a putative pathogenic point mutation, and 1 was compound heterozygous for 2 putative pathogenic point mutations. Functional studies of the variants were not performed. The patients were ascertained from a larger cohort of 94 GJB2/GJB6 (604418)-negative pediatric patients with sensorineural hearing loss who underwent genetic analysis. Vona et al. (2015) emphasized the difficulties in technical detection, evaluation, and interpretation of deletions and mutations in the STRC gene.