Journal of Molecular Medicine

, Volume 83, Issue 12, pp 1025–1032 | Cite as

A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome

  • E. KalayEmail author
  • A. P. M. de Brouwer
  • R. Caylan
  • S. B. Nabuurs
  • B. Wollnik
  • A. Karaguzel
  • J. G. A. M. Heister
  • H. Erdol
  • F. P. M. Cremers
  • C. W. R. J. Cremers
  • H. G. Brunner
  • H. Kremer
Original Article


Homozygosity mapping and linkage analysis in a Turkish family with autosomal recessive prelingual sensorineural hearing loss revealed a 15-cM critical region at 17q25.1–25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The maximum two-point lod score was 4.07 at θ=0.0 for the marker D17S801. The linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation analysis of USH1G led to the identification of a homozygous missense mutation D458V at the −3 position of the PDZ binding motif of SANS. This mutation was also present homozygously in one out of 64 additional families from Turkey with autosomal recessive nonsyndromic hearing loss and heterozygously in one out of 498 control chromosomes. By molecular modeling, we provide evidence that this mutation impairs the interaction of SANS with harmonin. Ophthalmologic examination and vestibular evaluation of patients from both families revealed mild retinitis pigmentosa and normal vestibular function. These results suggest that these patients suffer from atypical USH.


USH1G Retinal degeneration Atypical Usher syndrome SANS Deafness PDZ 



We are grateful to the members of the families for participating in this study. The authors thank E. Kandemir, E. Sözen for technical assistance, and C. Hoyng for valuable discussion. This study was supported by the Karadeniz Technical University Research Fund (project no. 2002.114.001.3), the Heinsius Houbolt Foundation, Stichting Irene Kinderziekenhuis, and Stichting Vrienden van Effatha.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • E. Kalay
    • 1
    • 2
    • 3
    Email author
  • A. P. M. de Brouwer
    • 1
    • 2
  • R. Caylan
    • 4
  • S. B. Nabuurs
    • 5
  • B. Wollnik
    • 6
  • A. Karaguzel
    • 3
  • J. G. A. M. Heister
    • 1
  • H. Erdol
    • 7
  • F. P. M. Cremers
    • 1
  • C. W. R. J. Cremers
    • 2
  • H. G. Brunner
    • 1
  • H. Kremer
    • 2
  1. 1.Department of Human GeneticsRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of OtorhinolaryngologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Department of Medical Biology and Genetics, Faculty of MedicineKaradeniz Technical UniversityTrabzonTurkey
  4. 4.Department of Otorhinolaryngology, Faculty of MedicineKaradeniz Technical UniversityTrabzonTurkey
  5. 5.Centre for Molecular and Biomolecular InformaticsRadboud University NijmegenNijmegenThe Netherlands
  6. 6.Center for Molecular Medicine Cologne (CMMC) and Institute of Human GeneticsUniversity of CologneCologneGermany
  7. 7.Department of Ophthalmology, Faculty of MedicineKaradeniz Technical UniversityTrabzonTurkey

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