Human Genetics

, Volume 128, Issue 1, pp 103–111

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

  • Katrin Friedrich
  • Lin Lee
  • Dru F. Leistritz
  • Gudrun Nürnberg
  • Bidisha Saha
  • Fuki M. Hisama
  • Daniel K. Eyman
  • Davor Lessel
  • Peter Nürnberg
  • Chumei Li
  • María J. Garcia-F-Villalta
  • Carolien M. Kets
  • Joerg Schmidtke
  • Vítor Tedim Cruz
  • Peter C. Van den Akker
  • Joseph Boak
  • Dincy Peter
  • Goli Compoginis
  • Kivanc Cefle
  • Sukru Ozturk
  • Norberto López
  • Theda Wessel
  • Martin Poot
  • P. F. Ippel
  • Birgit Groff-Kellermann
  • Holger Hoehn
  • George M. Martin
  • Christian Kubisch
  • Junko Oshima
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

Authors and Affiliations

  • Katrin Friedrich
    • 1
  • Lin Lee
    • 3
  • Dru F. Leistritz
    • 3
  • Gudrun Nürnberg
    • 2
  • Bidisha Saha
    • 3
  • Fuki M. Hisama
    • 4
  • Daniel K. Eyman
    • 3
  • Davor Lessel
    • 1
  • Peter Nürnberg
    • 2
  • Chumei Li
    • 5
  • María J. Garcia-F-Villalta
    • 6
  • Carolien M. Kets
    • 7
  • Joerg Schmidtke
    • 8
  • Vítor Tedim Cruz
    • 9
  • Peter C. Van den Akker
    • 10
  • Joseph Boak
    • 11
  • Dincy Peter
    • 12
  • Goli Compoginis
    • 13
  • Kivanc Cefle
    • 14
  • Sukru Ozturk
    • 14
  • Norberto López
    • 15
  • Theda Wessel
    • 16
  • Martin Poot
    • 17
  • P. F. Ippel
    • 17
  • Birgit Groff-Kellermann
    • 18
  • Holger Hoehn
    • 19
  • George M. Martin
    • 3
  • Christian Kubisch
    • 1
  • Junko Oshima
    • 3
  1. 1.Center for Molecular Medicine Cologne, Institute of Human Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)University of CologneCologneGermany
  2. 2.Center for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne Centre For GenomicsUniversity of CologneCologneGermany
  3. 3.Department of PathologyUniversity of WashingtonSeattleUSA
  4. 4.Department of MedicineUniversity of WahsigntonSeattleUSA
  5. 5.Toronto General HospitalTorontoCanada
  6. 6.Hospital de la PrincesaMadridSpain
  7. 7.Radboud UniversityNijmegenThe Netherlands
  8. 8.Institut für HumangenetikMedizinische HochschuleHannoverGermany
  9. 9.Hospital Sao SebastiaoSanta Maria da FeiraPortugal
  10. 10.Department of GeneticsUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands
  11. 11.Riverview Medical AssociatesRed BankUSA
  12. 12.Christian Medical CollegeVelloreIndia
  13. 13.University of Southern CaliforniaLos AngelesUSA
  14. 14.Istanbul Medical FacultyIstanbul UniversityIstanbulTurkey
  15. 15.Clinic Hospital Virgen de la VictoriaMalagaSpain
  16. 16.Department of Pediatric EndocrinologyCharité University HospitalBerlinGermany
  17. 17.Department of Medical GeneticsUniversity Medical Center UtrechtUtrechtThe Netherlands
  18. 18.Department of Dermatology and VenerologyKarl Landsteiner Institute for Dermatological ResearchSt. PoeltenAustria
  19. 19.Department of Human and Medical GeneticsUniversity of WürzburgWürzburgGermany