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Published January 1, 2009 | Version v1
Journal article Open

Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: A report of five novel mutations

Creators

  • 1. Ankara Univ, Sch Med, Dept Pediat, Div Clin Mol Pathol & Genet, Ankara, Turkey
  • 2. Dicle Univ, Sch Med, Dept Radiodiagnost, Diyarbakir, Turkey
  • 3. Baskent Univ, Sch Med Hosp, Dept Otorhinolaryngol, Konya, Turkey
  • 4. Eskisehir Osmangazi Univ, Sch Med, Dept Otorhinolaryngol, Eskisehir, Turkey
  • 5. Ankara Univ, Inst Biotechnol, Ankara, Turkey
  • 6. Vocat Sch Hlth, Dept Audiol, Ankara, Turkey
  • 7. Dicle Univ, Sch Med, Dept Otorhinolaryngol, Diyarbakir, Turkey
  • 8. Afyon Kocatepe Univ, Sch Med, Dept Otorhinolaryngol, Afyon, Turkey
  • 9. Baskent Univ, Sch Med, Dept Otorhinolaryngol, Adana, Turkey
  • 10. Ankara Univ, Sch Med, Dept Radiodiagnost, Ankara, Turkey
  • 11. Numune Hosp, Dept Otorhinolaryngol, Sivas, Turkey

Description

Genome wide homozygosity mapping using Affymetrix 10K arrays revealed the DFNB7/11 locus including the TMC1 gene in 5 of 35 Turkish families with autosomal recessive nonsyndromic severe to profound congenital or prelingual-onset sensorineural hearing loss (SNHL). Additional 51 families were later screened for co-segregation of the locus with the phenotype using microsatellite markers. GJB2 and mtDNA A1555G mutations were negative in probands from each family. Mutation analysis was performed in families showing co-segregation Of autosomal recessive SNHL with haplotypes at the DFNB7/11 locus. A total of six different mutations in seven families were identified, including novel missense alterations, p.G444R (c.1330G > A), p.R445C (c.1333C > T), and p.1677T (c.2030T > C), one novel splice site mutation IVS6+2 T > A (c.64+2T > A), and a novel large deletion ofapproximately 31 kb at the 3' region of the gene including exons 19-24, as well as a previously reported nonsense mutation, p.R34X (c.100C > T). All identified Mutations co-segregated with autosomal recessive SNHL in all families and were not found in Turkish hearing controls. These results expand the mutation spectrum of TMC1 with five novel mutations and provide data for the significant contribution of TMC1 mutations in hearing loss. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

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