Frequency and clinical features of hearing loss caused by STRC deletions

Abstract

Sensorineural hearing loss is a common deficit and mainly occurs due to genetic factors. Recently, copy number variants (CNVs) in the STRC gene have also been recognized as a major cause of genetic hearing loss. We investigated the frequency of STRC deletions in the Japanese population and the characteristics of associated hearing loss. For CNV analysis, we employed a specialized method of Ion AmpliSeqTM sequencing, and confirmed the CNV results via custom array comparative genomic hybridization. We identified 17 probands with STRC homozygous deletions. The prevalence of STRC homozygous deletions was 1.7% in the hearing loss population overall, and 4.3% among mild-to-moderate hearing loss patients. A 2.63% carrier deletion rate was identified in both the hearing loss and the control population with normal hearing. In conclusion, our results show that STRC deletions are the second most common cause of mild-to-moderate hearing loss after the GJB2 gene, which accounts for the majority of genetic hearing loss. The phenotype of hearing loss is congenital and appears to be moderate, and is most likely to be stable without deterioration even after the age of 50. The present study highlights the importance of the STRC gene as a major cause of mild-to-moderate hearing loss.

Molecular epidemiology of Chinese Han deaf patients with bi-allelic and mono-allelic GJB2 mutations

“…Among them, probands D908 and D2002 were found to carry homozygous deletions of the entire STRC gene (Additional file 1: Figure S1) and proband D1857 has a heterozygous deletion and a nonsense mutation c.3696G > A (p. W1232*) in STRC. Consistent with previous studies [17], all three probands with STRC homozygous or compound heterozygous deletions have moderate hearing loss (PTAs of 40-50 dB HL). Fourteen of the sixteen other independent mutations identified in this study have been reported to be associated with hearing loss in previous studies, including dominant mutations EYA1 c.1276G > A (p. G426S) [18] and MITF c.877C > T (p. R293*) [19], recessive mutations PCDH15 c.4133C > T (p. T1378I) and c.1453delT (p. S485Rfs*2) [20], USH2A c.10904C > A (p.T3635 N) [21], MYO15A c.8158G > A (p. D2720N) and c.10258_10260delTTC (p.F3420-) [22], CDH23 c.7630 T > G (p. L2544 V) and c.8257G > A (p.A2753T) [20], OTOF c.2122C > T (p.R708*) and c.1194 T > A (p.D398E) [23,24], SLC26A4 c.1174A > T (p. N392Y) and c.1975G > C (p.V659 L) [25], and SMPX c.55A > G (p. N19D) [26].…”

Otogelin, otogelin-like, and stereocilin form links connecting outer hair cell stereocilia to each other and the tectorial membrane

“…In the absence of stereocilin, OHC stereocilia are not connected to one another, and the tall stereocilia are not anchored into the TM, resulting in OHC dysfunction but with no deleterious effect on IHCs (10,11). DFNB16 patients suffer from mild-to-moderate hearing impairment that is more pronounced at high sound frequencies than at low sound frequencies (12)(13)(14)(15)(16)(17). This auditory phenotype is uncommon among patients with DFNB (nonsyndromic deafness, autosomal recessive) forms of prelingual hearing impairment, who usually suffer from severe or profound deafness as a result of primary defects of both types of hair cells, IHCs alone, or nonsensory (supporting) cells.…”

Lights and Shadows in the Genetics of Syndromic and Non-Syndromic Hearing Loss in the Italian Population

“…The possibility to simultaneously screen large number of genes is essential to address with the genetic heterogeneity of HHL. This aspect is fundamental for NSHL, where, apart from the relevant contribution of the GJB2 gene and, in some populations of GJB6 gene, both responsible for ~50% of all AR cases [ 14 , 15 , 16 ], and of STRC deletions (accounting for 1% to 5% of HL cases [ 17 ]), no other worldwide primary players have been identified.…”