Original Investigation

Human Genetics

, Volume 128, Issue 1, pp 103-111

First online:

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

  • Katrin FriedrichAffiliated withCenter for Molecular Medicine Cologne, Institute of Human Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
  • , Lin LeeAffiliated withDepartment of Pathology, University of Washington
  • , Dru F. LeistritzAffiliated withDepartment of Pathology, University of Washington
  • , Gudrun NürnbergAffiliated withCenter for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne Centre For Genomics, University of Cologne
  • , Bidisha SahaAffiliated withDepartment of Pathology, University of Washington
  • , Fuki M. HisamaAffiliated withDepartment of Medicine, University of Wahsignton
  • , Daniel K. EymanAffiliated withDepartment of Pathology, University of Washington
  • , Davor LesselAffiliated withCenter for Molecular Medicine Cologne, Institute of Human Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
  • , Peter NürnbergAffiliated withCenter for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne Centre For Genomics, University of Cologne
    • , Chumei LiAffiliated withToronto General Hospital
    • , María J. Garcia-F-VillaltaAffiliated withHospital de la Princesa
    • , Carolien M. KetsAffiliated withRadboud University
    • , Joerg SchmidtkeAffiliated withInstitut für Humangenetik, Medizinische Hochschule
    • , Vítor Tedim CruzAffiliated withHospital Sao Sebastiao
    • , Peter C. Van den AkkerAffiliated withDepartment of Genetics, University Medical Center Groningen, University of Groningen
    • , Joseph BoakAffiliated withRiverview Medical Associates
    • , Dincy PeterAffiliated withChristian Medical College
    • , Goli CompoginisAffiliated withUniversity of Southern California
    • , Kivanc CefleAffiliated withIstanbul Medical Faculty, Istanbul University
    • , Sukru OzturkAffiliated withIstanbul Medical Faculty, Istanbul University
    • , Norberto LópezAffiliated withClinic Hospital Virgen de la Victoria
    • , Theda WesselAffiliated withDepartment of Pediatric Endocrinology, Charité University Hospital
    • , Martin PootAffiliated withDepartment of Medical Genetics, University Medical Center Utrecht
    • , P. F. IppelAffiliated withDepartment of Medical Genetics, University Medical Center Utrecht
    • , Birgit Groff-KellermannAffiliated withDepartment of Dermatology and Venerology, Karl Landsteiner Institute for Dermatological Research
    • , Holger HoehnAffiliated withDepartment of Human and Medical Genetics, University of Würzburg
    • , George M. MartinAffiliated withDepartment of Pathology, University of Washington
    • , Christian KubischAffiliated withCenter for Molecular Medicine Cologne, Institute of Human Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
    • , Junko OshimaAffiliated withDepartment of Pathology, University of Washington Email author 

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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.