Journal of Molecular Medicine

, Volume 80, Issue 2, pp 124–131 | Cite as

Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients

  • Marie Wattenhofer
  • Mario Di Iorio
  • Raquel Rabionet
  • Loretta Dougherty
  • Andreas Pampanos
  • Torsten Schwede
  • Barbara Montserrat-Sentis
  • Maria Arbones
  • Theofilos Iliades
  • Annamaria Pasquadibisceglie
  • Marcello D'Amelio
  • Sura Alwan
  • Colette Rossier
  • Hans-Henrik M. Dahl
  • Michael B. Petersen
  • Xavier Estivill
  • Paolo Gasparini
  • Hamish S. Scott
  • Stylianos E. Antonarakis
Original Article

Abstract.

Two loci for nonsyndromic recessive deafness located on chromosome 21q22.3 have previously been reported, DFNB8 and DFNB10. Recently a gene which encodes a transmembrane serine protease, TMPRSS3 or ECHOS1, was found to be responsible for both the DFNB8 and DFNB10 phenotypes. To determine the contribution of TMPRSS3 mutations in the general congenital/childhood nonsyndromic deaf population we performed mutation analysis of the TMPRSS3 gene in 448 unrelated deaf patients from Spain, Italy, Greece, and Australia who did not have the common 35delG GJB2 mutation. From the 896 chromosomes studied we identified two novel pathogenic mutations accounting for four mutant alleles and at least 16 nonpathogenic sequence variants. The pathogenic mutations were a 1-bp deletion resulting in a frameshift and an amino acid substitution in the LDLRA domain of TMPRSS3. From this and another study we estimate the frequency of TMPRSS3 mutations in our sample as 0.45%, and approximately 0.38% in the general Caucasian childhood deaf population. However, TMPRSS3 is still an important contributor to genetic deafness in populations with large consanguineous families.

Deafness TMPRSS3 Caucasians Chromosome 21 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Marie Wattenhofer
    • 1
  • Mario Di Iorio
    • 2
  • Raquel Rabionet
    • 3
  • Loretta Dougherty
    • 4
  • Andreas Pampanos
    • 5
  • Torsten Schwede
    • 6
  • Barbara Montserrat-Sentis
    • 3
  • Maria Arbones
    • 3
  • Theofilos Iliades
    • 7
  • Annamaria Pasquadibisceglie
    • 8
  • Marcello D'Amelio
    • 2
  • Sura Alwan
    • 1
  • Colette Rossier
    • 1
  • Hans-Henrik M. Dahl
    • 9
  • Michael B. Petersen
    • 5
  • Xavier Estivill
    • 3
  • Paolo Gasparini
    • 8
  • Hamish S. Scott
    • 4
  • Stylianos E. Antonarakis
    • 1
  1. 1.Division of Medical Genetics, University of Geneva Medical School, 1, Rue Michel-Servet, 1211 Geneva 4Switzerland
  2. 2.Telethon Institute of Genetics and Medicine (TIGEM), NaplesItaly
  3. 3.Medical and Molecular Genetics Center, Institut de Recerca Oncologica, BarcelonaSpain
  4. 4.Genetics and Bioinformatics Division, the Walter and Eliza Hall Institute of Medical Research, Royal Melbourne HospitalAustralia
  5. 5.Institute of Child Health, Athens, Greece
  6. 6.GlaxoSmithKline R&D, World Trade Center I, GenevaSwitzerland
  7. 7.Otolaryngology Department, Aristotle University of Thessaloniki, Greece
  8. 8.Medical Genetics Service, IRCCS-CSS, San Giovanni Rotondo, Italy
  9. 9.Murdoch Childrens Research Institute, Royal Children's Hospital, MelbourneAustralia

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