WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations.
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.
Friedrich
Katrin
K
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.
Lee
Lin
L
Leistritz
Dru F
DF
Nürnberg
Gudrun
G
Saha
Bidisha
B
Hisama
Fuki M
FM
Eyman
Daniel K
DK
Lessel
Davor
D
Nürnberg
Peter
P
Li
Chumei
C
Garcia-F-Villalta
María J
MJ
Kets
Carolien M
CM
Schmidtke
Joerg
J
Cruz
Vítor Tedim
VT
Van den Akker
Peter C
PC
Boak
Joseph
J
Peter
Dincy
D
Compoginis
Goli
G
Cefle
Kivanc
K
Ozturk
Sukru
S
López
Norberto
N
Wessel
Theda
T
Poot
Martin
M
Ippel
P F
PF
Groff-Kellermann
Birgit
B
Hoehn
Holger
H
Martin
George M
GM
Kubisch
Christian
C
Oshima
Junko
J
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
D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase