title: WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations.
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.
authors.affiliation: Center for Molecular Medicine Cologne, Institute of Human Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Friedrich
authors.forename: Lin
authors.initials: L
authors.lastname: Lee
authors.forename: Dru F
authors.initials: DF
authors.lastname: Leistritz
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: Bidisha
authors.initials: B
authors.lastname: Saha
authors.forename: Fuki M
authors.initials: FM
authors.lastname: Hisama
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Eyman
authors.forename: Davor
authors.initials: D
authors.lastname: Lessel
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Chumei
authors.initials: C
authors.lastname: Li
authors.forename: María J
authors.initials: MJ
authors.lastname: Garcia-F-Villalta
authors.forename: Carolien M
authors.initials: CM
authors.lastname: Kets
authors.forename: Joerg
authors.initials: J
authors.lastname: Schmidtke
authors.forename: Vítor Tedim
authors.initials: VT
authors.lastname: Cruz
authors.forename: Peter C
authors.initials: PC
authors.lastname: Van den Akker
authors.forename: Joseph
authors.initials: J
authors.lastname: Boak
authors.forename: Dincy
authors.initials: D
authors.lastname: Peter
authors.forename: Goli
authors.initials: G
authors.lastname: Compoginis
authors.forename: Kivanc
authors.initials: K
authors.lastname: Cefle
authors.forename: Sukru
authors.initials: S
authors.lastname: Ozturk
authors.forename: Norberto
authors.initials: N
authors.lastname: López
authors.forename: Theda
authors.initials: T
authors.lastname: Wessel
authors.forename: Martin
authors.initials: M
authors.lastname: Poot
authors.forename: P F
authors.initials: PF
authors.lastname: Ippel
authors.forename: Birgit
authors.initials: B
authors.lastname: Groff-Kellermann
authors.forename: Holger
authors.initials: H
authors.lastname: Hoehn
authors.forename: George M
authors.initials: GM
authors.lastname: Martin
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.forename: Junko
authors.initials: J
authors.lastname: Oshima
mesh_terms: D056905:Chromosome Breakpoints; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D053484:RecQ Helicases / Q000235:genetics*; D014898:Werner Syndrome / Q000235:genetics*; D000071657:Werner Syndrome Helicase
chemical_list: D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase