J Med Genet 40:360-363 doi:10.1136/jmg.40.5.360
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Distinctive audiometric profile associated with DFNB21 alleles of TECTA

  1. S Naz1,2,
  2. F Alasti2,3,
  3. A Mowjoodi1,2,3,*,
  4. S Riazuddin1,2,
  5. M H Sanati3,
  6. T B Friedman2,
  7. A J Griffith2,
  8. E R Wilcox2,
  9. S Riazuddin1,2
  1. 1National Centre of Excellence in Molecular Biology, Lahore, Pakistan
  2. 2Laboratory of Molecular Genetics, National Institute on Deafness and other Communication Disorders, NIH, Rockville, MD 20850, USA
  3. 3National Research Centre for Genetic Engineering and Biotechnology, Tehran, Iran
  1. Correspondence to:
 Dr Sheikh Riazuddin, National Centre of Excellence in Molecular Biology, Canal Bank Road, Thokar Niaz Baig Lahore-53700, Pakistan; 

    Genetic factors are thought to account for approximately one half of cases of childhood hearing loss, the majority of which is non-syndromic and not associated with other abnormalities. Seventy-seven percent of hereditary, non-syndromic, prelingual deafness is autosomal recessive, 22% is autosomal dominant, and 1% is transmitted as a matrilineal or X linked trait.1 So far, more than 30 distinct genetic loci (known as DFNB loci) have been mapped for non-syndromic recessive deafness (NSRD). In the absence of syndromic associations to guide genetic diagnosis, the auditory and vestibular features provide the only phenotypic clues to direct molecular diagnostic testing. Unfortunately, the phenotype of NSRD is usually non-specific; prelingual, non-progressive, and severe-profound impairment is associated with mutations in a majority of DFNB loci.2 In contrast, inherited dominant hearing loss is more phenotypically heterogeneous; it is usually postlingual, progressive, and can be associated with a variety of different audiometric configurations.2

    Mutations in the gene encoding α-tectorin (TECTA) are associated with both dominant and recessive modes of inherited hearing loss, DFNA8/A12 (MIM 601543 and MIM 601842) and DFNB21 (MIM 603629), respectively, and provide a robust model of genotype-phenotype correlation. Missense substitutions in TECTA result in dominant hearing loss (table 1). Three of these missense dominant alleles result in substitution of cysteine residues and are associated with progressive hearing loss.3–5 All other dominant missense alleles of TECTA are associated with stable, non-progressive hearing loss.6,7 The only known recessive allele of TECTA is a splice site mutation that causes prelingual, severe-profound deafness linked to DFNB21.8

    View this table:
    Table 1

    TECTA mutations and associated phenotype

    α-tectorin is one of the major glycoproteins of the tectorial membrane, the acellular matrix overlying the cochlear neuroepithelium.9,10 α-tectorin has predicted structural domains with similarity to protein modules important for cross linking with other proteins.6,