Prevalence of TECTA mutation in patients with mid-frequency sensorineural hearing loss

Abstract

BackgroundTo date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL.MethodsSubjects with bilateral non-syndromic hearing loss were prescreened for GJB2 and m.1555A > G and m.3243A > G mitochondrial DNA mutations, and patients with inner ear malformations were excluded. We selected MFSNHL patients whose audiograms met the U-shaped criterion proposed by the GENDEAF study group, along with those with shallow U-shaped audiograms, for TECTA analysis. All TECTA exons were analyzed by Sanger sequencing. Novel missense variants were classified as possibly pathogenic, non-pathogenic, and variants of uncertain significance, based on genetic data. To evaluate novel possibly pathogenic variants, we predicted changes in protein structure by molecular modeling.ResultsPathogenic and possibly pathogenic variants of TECTA were found in 4 (6.0%) of 67 patients with MFSNHL. In patients with U-shaped audiograms, none (0%) of 21 had pathogenic or possibly pathogenic variants. In patients with shallow U-shaped audiograms, four (8.7%) of 46 had pathogenic or possibly pathogenic variants. Two novel possibly pathogenic variants were identified and two previously reported mutations were considered as variant of unknown significance. The clinical features of patients with pathogenic and possibly pathogenic variants were consistent with those in previous studies. Pathogenic or possibly pathogenic variants were identified in 3 of 23 families (13.0%) which have the family histories compatible with autosomal dominant and 1 of 44 families (2.3%) which have the family histories compatible with sporadic or autosomal recessive.Conclusions TECTA mutations were identified in 6.0% of MFSNHL. These mutations were more frequent in patients with shallow U-shaped audiograms than those with U-shaped audiograms, and in families which have the family histories compatible with autosomal dominant than those with the family histories compatible with sporadic or autosomal recessive.Electronic supplementary materialThe online version of this article (10.1186/s13023-017-0708-z) contains supplementary material, which is available to authorized users.

The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss

“…Among those genes, mutations in TECTA are the most frequent cause of mid-frequency HL [1,24,33,34]. Yamamoto et al reported that pathogenic and possibly pathogenic variants of TECTA were found in 6.0% of mid-frequency SNHL patients [35].…”

Elongated EABR wave latencies observed in patients with auditory neuropathy caused by OTOF mutation

“…Deafness genes were tested at the Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center by the Sanger method using the genomic DNA extracted from patients' peripheral blood cells when their deafness genes have not been clarified by previous genetic testing performed by BML supported by National Health Insurance. We performed the Sanger methods as previously reported . Genes and mutations of the enrolled patients are shown in Supplementary Table I.…”

“…We performed the Sanger methods as previously reported. 15,34,35 Genes and mutations of the enrolled patients are shown in Supplementary Table I.…”

Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1

“…TECTA can be responsible for autosomal dominant or autosomal recessive hearing loss. Among families with dominant hearing loss, missense mutations in the TECTA zonadhesion domain (amino acid residues 260‐1694) are associated with high‐frequency hearing loss, while missense mutations in the TECTA zona pellucida domain (residues 1795‐2059) are associated with mid‐frequency hearing impairment 35‐37 . This correspondence obtains for family HL277 (p.Ala963Thr) and family DF193 (p.Asp2006Gly) (Figure S1).…”