Association of clinical features with mutation of TECTA in a family with autosomal dominant hearing loss

Background: The TECTA gene, which encodes alpha-tectorin, has recently been cloned. alpha-Tectorin is a major component of the noncollagenous matrix of the tectorial membrane. Nonsyndromic hearing impairment caused by TECTA mutations has been reported in Austrian, Belgian, Swedish, French, and Lebanese families. The phenotypes and genotypes were different among these families. Materials and Methods: Our study family displayed autosomal dominant hearing impairment through 3 generations. We sequenced the coding exons of the TECTA gene in 4 affected individuals, and we report the clinical features in a Japanese family with nonsyndromic hearing impairment and a mutation in the TECTA gene. Results: The 5-frequency average of 250, 500, 1000, 2000, and 4000 Hz in 4 affected individuals was 42.2 +/- 3.7 (mean +/- SD) dB in the right ear and 42.3 +/- 4.5 dB in the left ear. The mean age at onset of hearing impairment was 5 years. The progression of hearing impairment was not confirmed for a 15-year, period, from the age of 6 to 21 years, in 1 affected member. The 4 patients had a G-->A missense mutation at nucleotide 6063 in exon 20. This mutation replaces arginine at residue 2021 with histidine (R2021H). Conclusions: All 4 affected members showed symmetrical and stable bilateral mild to moderate hearing impairment in the midfrequencies. The mean threshold level of 2000 Hz was the worst among the 5 frequencies. All the affected members had normal vestibular function. The mutation in the TECTA gene, localized in the zona pellucida domain, was detected in all 4 affected individuals. The localization of the mutation in the different modules of the protein may have caused the different clinical features.