Human Genetics

, Volume 128, Issue 1, pp 103–111

WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations

Authors

  • Katrin Friedrich
    • Center for Molecular Medicine Cologne, Institute of Human Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)University of Cologne
  • Lin Lee
    • Department of PathologyUniversity of Washington
  • Dru F. Leistritz
    • Department of PathologyUniversity of Washington
  • Gudrun Nürnberg
    • Center for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne Centre For GenomicsUniversity of Cologne
  • Bidisha Saha
    • Department of PathologyUniversity of Washington
  • Fuki M. Hisama
    • Department of MedicineUniversity of Wahsignton
  • Daniel K. Eyman
    • Department of PathologyUniversity of Washington
  • Davor Lessel
    • Center for Molecular Medicine Cologne, Institute of Human Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)University of Cologne
  • Peter Nürnberg
    • Center for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne Centre For GenomicsUniversity of Cologne
  • Chumei Li
    • Toronto General Hospital
  • María J. Garcia-F-Villalta
    • Hospital de la Princesa
  • Carolien M. Kets
    • Radboud University
  • Joerg Schmidtke
    • Institut für HumangenetikMedizinische Hochschule
  • Vítor Tedim Cruz
    • Hospital Sao Sebastiao
  • Peter C. Van den Akker
    • Department of GeneticsUniversity Medical Center Groningen, University of Groningen
  • Joseph Boak
    • Riverview Medical Associates
  • Dincy Peter
    • Christian Medical College
  • Goli Compoginis
    • University of Southern California
  • Kivanc Cefle
    • Istanbul Medical FacultyIstanbul University
  • Sukru Ozturk
    • Istanbul Medical FacultyIstanbul University
  • Norberto López
    • Clinic Hospital Virgen de la Victoria
  • Theda Wessel
    • Department of Pediatric EndocrinologyCharité University Hospital
  • Martin Poot
    • Department of Medical GeneticsUniversity Medical Center Utrecht
  • P. F. Ippel
    • Department of Medical GeneticsUniversity Medical Center Utrecht
  • Birgit Groff-Kellermann
    • Department of Dermatology and VenerologyKarl Landsteiner Institute for Dermatological Research
  • Holger Hoehn
    • Department of Human and Medical GeneticsUniversity of Würzburg
  • George M. Martin
    • Department of PathologyUniversity of Washington
  • Christian Kubisch
    • Center for Molecular Medicine Cologne, Institute of Human Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)University of Cologne
    • Department of PathologyUniversity of Washington
Original Investigation

DOI: 10.1007/s00439-010-0832-5

Cite this article as:
Friedrich, K., Lee, L., Leistritz, D.F. et al. Hum Genet (2010) 128: 103. doi:10.1007/s00439-010-0832-5

Abstract

Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by null mutations at the WRN locus, which codes for a member of the RecQ family of DNA helicases. Since 1988, the International Registry of Werner syndrome had enrolled 130 molecularly confirmed WS cases from among 110 worldwide pedigrees. We now report 18 new mutations, including two genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and two rare missense mutations. We also review evidence for founder mutations among various ethnic/geographic groups. Founder WRN mutations had been previously reported in Japan and Northern Sardinia. Our Registry now suggests characteristic mutations originated in Morocco, Turkey, The Netherlands and elsewhere.

Supplementary material

439_2010_832_MOESM1_ESM.doc (288 kb)
Supplementary material 1 (DOC 287 kb)

Copyright information

© Springer-Verlag 2010