MY015A (DFNB3) mutations in Turkish hearing loss families and functional modeling of a novel motor domain mutation


Kalay E., Üzümcü A., KRIEGER E., CAYLAN R., UYGUNER O., Ulubil-Emiroğlu M., ...Daha Fazla

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, ss.2382-2389, 2007 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: Konu: 20
  • Basım Tarihi: 2007
  • Doi Numarası: 10.1002/ajmg.a.31937
  • Dergi Adı: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
  • Sayfa Sayıları: ss.2382-2389

Özet

Myosin XVA is an unconventional myosin which has been implicated in autosomal recessive nonsyndromic hearing impairement (ARNSHI) in humans. In Myo15A mouse models, vestibular dysfunction accompanies the autosomal recessive hearing loss. Genomewide homozygosity mapping and subsequent fine mapping in two Turkish families with ARNSHI revealed significant linkage to a critical interval harbouring a known deafness gene MYO15A on chromosome 17p13.1-17q11.2. Subsequent sequencing of the MYO15A gene led to the identification of a novel missense mutation, c.5492G-T(p.Gly1831Val) and a novel missense mutation, c.5492G-T (p.Gly1831Val) and a novel splice site mutation,c.8968-1G-C. These mutations were not detected in additional 64 unrelated ARNSHI index patients and in 230 Turkish control chromosomes. Gly1831 is a conserved residue located in the motor domains of the different classes of myosins of different species. Molecular modeling of the motor head domain of the human myosin XVa protein suggests that the Gly1831Val mutation inhibits the power-stroke by reducing backbone flexibility and weakening the hydrophobic interactions necessary for signal transmission to the converter domain. (C) 2007Wiley-Liss, Inc.