Identification of a Novel TECTA mutation in a Chinese DFNA8/12 family with prelingual progressive sensorineural hearing impairment

PLoS One. 2013 Jul 31;8(7):e70134. doi: 10.1371/journal.pone.0070134. Print 2013.

Abstract

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 TECTA, 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 TECTA 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 TECTA mutation identified in Chinese population. Our data provides additional molecular and clinical information for establishing a better genotype-phenotype understanding of DFNA8/12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Amino Acid Sequence
  • Asian People / genetics
  • Base Sequence
  • Child
  • China
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11 / genetics
  • DNA Mutational Analysis
  • Deafness / ethnology
  • Deafness / genetics*
  • Deafness / pathology
  • Extracellular Matrix Proteins / genetics*
  • Family Health
  • Female
  • GPI-Linked Proteins / genetics
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Hearing Loss, Sensorineural / ethnology
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / pathology
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense*
  • Pedigree
  • Sequence Homology, Amino Acid
  • Young Adult

Substances

  • Extracellular Matrix Proteins
  • GPI-Linked Proteins
  • TECTA protein, human

Grants and funding

These investigations were supported by Key Project of National Natural Science Foundation of China (81030017), National Science Fund for Distinguished Young Scholars (81125008) to HJ Yuan and The National Basic Research Program (2013CB945402) to DY Han and HJ Yuan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.