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

Abstract

TECTA is well known as a causative gene for autosomal dominant mid-frequency hearing loss observed in various populations. In this study, we performed next-generation sequencing analysis of a large Japanese hearing loss cohort, including eight hundred and twelve (812) subjects from unrelated autosomal dominant hearing loss families, to estimate the prevalence and phenotype-genotype correlations in patients with TECTA mutations. The prevalence of TECTA mutations in Japanese autosomal dominant sensorineural hearing loss families was found to be 3.2%. With regard to the type of hearing loss, the patients with mutations in the nidogen-like domain or ZA domain of TECTA showed varied audiograms. However, most of the patients with mutations in the ZP domain showed mid-frequency hearing loss. The rate of hearing deterioration in TECTA-associated hearing loss patients and in the normal hearing Japanese control population were the same and regression lines for each group were parallel. We carried out haplotype analysis for four families which had one recurring missense variant, c.5597C>T (p.Thr1866Met). Our results revealed four different haplotypes, suggesting that this mutation occurred independently in each family. In conclusion, TECTA variants represent the second largest cause of autosomal dominant sensorineural hearing loss in Japan. The hearing loss progression observed in the patients with TECTA mutations might reflect presbycusis. The c.5597C>T mutation occurred in a mutational hot spot and is observed in many ethnic populations.

Keywords: DFNA8/12; TECTA; autosomal dominant; genotype-phenotype correlation; haplotype analysis; hearing progression; non-syndromic hearing loss; prevalence.

Figure 1

Pedigree and audiograms for each family with TECTA variants listed in Table 1. Arrows indicate the probands in each family. Genetic findings for each individual tested are noted in the pedigree. NIDO: nidogen-like domain, ZA: zonahesin-like domain, ZP: zona pellucida domain. Circle and solid line: right ear hearing threshold, X-mark and dotted line: left ear hearing threshold.

Figure 1

Pedigree and audiograms for each family with TECTA variants listed in Table 1. Arrows indicate the probands in each family. Genetic findings for each individual tested are noted in the pedigree. NIDO: nidogen-like domain, ZA: zonahesin-like domain, ZP: zona pellucida domain. Circle and solid line: right ear hearing threshold, X-mark and dotted line: left ear hearing threshold.

Figure 1

Pedigree and audiograms for each family with TECTA variants listed in Table 1. Arrows indicate the probands in each family. Genetic findings for each individual tested are noted in the pedigree. NIDO: nidogen-like domain, ZA: zonahesin-like domain, ZP: zona pellucida domain. Circle and solid line: right ear hearing threshold, X-mark and dotted line: left ear hearing threshold.

Figure 1

Pedigree and audiograms for each family with TECTA variants listed in Table 1. Arrows indicate the probands in each family. Genetic findings for each individual tested are noted in the pedigree. NIDO: nidogen-like domain, ZA: zonahesin-like domain, ZP: zona pellucida domain. Circle and solid line: right ear hearing threshold, X-mark and dotted line: left ear hearing threshold.

Figure 2

(a) Domain structure of α-tectorin and the overlapping audiograms from the better hearing ear for the patients with each domain variant. Yellow lines indicate the candidate VUS variants, and red lines indicate the likely pathogenic variants. (b) The overlapping audiograms for the patients that were reported variants of TECTA in previously. NIDO: Nidogen-like domain, ZA: Zonahesin-like domain, C: Von Willebrand factor C domain, T(n): Trypsin inhibitor-like domain (number), VWD: Von Willebrand factor D domain, ZP: Zona pellucida domain.

Figure 3

Detailed progression analysis of HL deterioration for patients with TECTA mutations. Lines indicate the linear regression for each group. Blue dots indicate the pure-tone average (PTA) of each patient with TECTA variants. Red dots indicating the PTA for Japanese normal hearing control population (Tsuiki et al. Audiology Japan 2003, 46, 235–240, in Japanese).