Human Genetics

, Volume 101, Issue 2, pp 229–234

Novel stop and frameshifting mutations in the autosomal dominant polycystic kidney disease 2 (PKD2) gene

Authors

  • Miguel Viribay
    • Unidad de Genética Molecular, Hospital Ramón y Cajal, Crtra. Colmenar Km 9.1, E-28034 Madrid, Spain Fax: +34-1-3369016; e-mail: jose.l.sanmillan@hrc.es
  • Tomohito Hayashi
    • Departments of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY
  • Dolores Tellería
    • Unidad de Genética Molecular, Hospital Ramón y Cajal, Crtra. Colmenar Km 9.1, E-28034 Madrid, Spain Fax: +34-1-3369016; e-mail: jose.l.sanmillan@hrc.es
  • Toshio Mochizuki
    • Departments of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY
  • David M. Reynolds
    • Departments of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY
  • Rafael Alonso
    • Servicio de Nefrología, Hospital Clínico Universitario, Santiago de Compostela, Galicia, Spain
  • Xose M. Lens
    • Servicio de Nefrología, Hospital Clínico Universitario, Santiago de Compostela, Galicia, Spain
  • Felipe Moreno
    • Unidad de Genética Molecular, Hospital Ramón y Cajal, Crtra. Colmenar Km 9.1, E-28034 Madrid, Spain Fax: +34-1-3369016; e-mail: jose.l.sanmillan@hrc.es
  • Peter C. Harris
    • MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
  • Stefan Somlo
    • Departments of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY
  • José L. San Millán
    • Unidad de Genética Molecular, Hospital Ramón y Cajal, Crtra. Colmenar Km 9.1, E-28034 Madrid, Spain Fax: +34-1-3369016; e-mail: jose.l.sanmillan@hrc.es
Original investigation

DOI: 10.1007/s004390050621

Cite this article as:
Viribay, M., Hayashi, T., Tellería, D. et al. Hum Genet (1997) 101: 229. doi:10.1007/s004390050621

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent inherited disorders. The majority of cases are due to mutation of the PKD1 gene, on 16p13.3, while in most of the remainder the disease maps to the PKD2 locus, at chromosome 4q21-q23. Recently, the PKD2 gene has been positionally cloned and three nonsense mutations within the coding sequence of the gene identified. Here we report a systematic mutation screening of all 15 exons of the PKD2 gene in chromosome 4-linked ADPKD families, using heteroduplex and SSCP analyses. We have identified and characterized seven novel mutations, with a detection rate of approximately 90% in the population studied. All of the mutations result in the premature stop of translation: four nonsense changes and three deletions. The deletions are all frameshifting, of four T nucleotides in one case and one G nucleotide in the other two. All mutations are unique and are distributed throughout the gene without evidence of clustering. Comparison of specific mutations with the clinical profile in ADPKD2 families shows no clear correlation.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997