Identification of a Novel <i>TECTA</i> Mutation in a Chinese DFNA8/12 Family with Prelingual Progressive Sensorineural Hearing Impairment

<div><p>Tectorial membrane, an extracellular matrix of the cochlea, plays a crucial role in the transmission of sound to the sensory hair cells. Alpha-tectorin is the most important noncollagenous component of the tectorial membrane and the otolith membrane in the maculae of the vestibular system. Defects in <i>TECTA</i>, the gene encodes alpha-tectorin, are cause of both dominant (DFNA8/12) and recessive (DFNB21) forms of deafness. Here, we report a three-generation Chinese family characterized by prelingual progressive sensorineural hearing impairment. We mapped the disease locus to chromosome 11q23-24 region, overlapping with the DFNA8/12 locus. Sequencing of candidate gene <i>TECTA</i> revealed a heterozygous c.5945C>A substitution in exon 19, causing amino acid substitution of Ala to Asp at a conservative position 1982. The A1982D substitution is consistent with hearing loss in this Chinese family and has not been found in 200 random control chromosomes. To our knowledge, this is the first <i>TECTA</i> mutation identified in Chinese population. Our data provides additional molecular and clinical information for establishing a better genotype–phenotype understanding of DFNA8/12.</p></div

Pedigree of three-generation Chinese family GD-O031 with prelingual progressive hearing impairment and audiograms of 11 affected subjects.

<p>Affected subjects are denoted in black. Based on the audiograms of the affected subjects (red, right ear; black, left ear), the severity of hearing impairment was moderate to severe and progress slowly with increasing patient age. The hearing loss involved all frequencies.</p

Mutation analysis of the Chinese family GD-O031.

<p>a. DNA sequence chromatograms showing heterozygous missense c.5945C>A mutation, compared to wild-type controls. The structure of TECTA depicts the position of c.5945C>A mutation in exon 19 and p.A1982D in ZP domain. b. Conservation analysis shows that the Ala residue at 1982 in TECTA is conserved across human, chimpanzee, mouse, chicken, and fish.</p