Novel <b><i>TECTA </i></b>Mutations Identified in Stable Sensorineural Hearing Loss and Their Clinical Implications

Abstract

TECTA is a causative gene of autosomal dominant (DFNA8/A12) and autosomal recessive (DFNB 21) nonsyndromic sensorineural hearing loss (NSHL). Mutations in TECTA account for 4% of all autosomal dominant NSHL cases in some populations and are thus thought to be one of the major causes of autosomal dominant NSHL. A genotype-phenotype correlation for autosomal dominant mutations in the TECTA gene has been proposed. Two families (SB146 and SB149), which segregated moderate NSHL in an autosomal dominant fashion, were included in this study. We performed targeted resequencing of 134 known deafness genes (TRS-134) and bioinformatics analyses to find causative mutations for NSHL in these 2 families. Through TRS-134, we detected 2 novel mutations, i.e. c.3995G>T (p.C1332F) and c.5618C>T (p.T1873I), in the TECTA gene. These mutations cosegregated with NSHL in the studied families and were not detected in normal controls. The mutations c.3995G>T and c.5618C>T reside in the von Willebrand factor type D3-D4 (vWFD3-D4) interdomain of the zonadhesin (ZA) domain and the zona pellucida (ZP) domain, respectively. p.C1332F is the first mutation detected in the vWFD3-D4 interdomain of the ZA domain. The mutations p.C1332F and p.T1873I were associated with stable high-frequency and mid-frequency hearing loss, respectively. Notably, the cysteine residue mutated to phenylalanine in SB146 was not related to progression of sensorineural hearing loss, which argues against the previous hypothesis. Here we confirm a known genotype-phenotype correlation for the ZP domain and propose a hypothetical genotype-phenotype correlation which relates mutations in vWFD3-D4 to stable high-frequency NSHL in Koreans. This clinical feature makes subjects with the missense mutation in the vWFD3-D4 interdomain of TECTA potentially good candidates for middle ear implantation. i 2014 S. Karger AG, Basel

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

“…Interestingly, the c.3995G>A variant identified in this study caused a p.Cys1332Tyr amino acid change. Kim et al have reported the c.3995G>T variant as pathogenic, which despite having a different nucleotide change, resulted in the same amino acid change [28].…”

A Novel S100A8/A9 Induced Fingerprint of Mesenchymal Stem Cells associated with Enhanced Wound Healing

“…α-tectorin is a major non-collagenous connective tissue component of the tectorial membrane in the inner ear. Mutations in the TECTA gene have been reported to be responsible for autosomal dominant non-syndromic hearing impairment and a recessively inherited disorder of sensorineural pre-lingual non-syndromic deafness 54 , 55 . It is most interesting that TECTA which - to the best of our knowledge - has not been described in MSCs nor in the skin is induced in S100A8/9 treated MSCs.…”

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).…”