title: Recent Trends in WRN Gene Mutation Patterns in Individuals with Werner Syndrome.
abstract: OBJECTIVE
  To determine recent trends in mutation patterns in the WRN gene, which cause Werner syndrome (WS), a rare, inheritable progeroid syndrome in Japan.
  
  
  METHODS
  Retrospective cohort.
  
  
  METHODS
  Longitudinal survey of WS and literature search for case reports.
  
  
  METHODS
  Individuals whose genetic testing their facilities had requested between 2009 and October 2016 (N = 67).
  
  
  METHODS
  A nationwide epidemiological study was conducted from 2009 to 2011 to improve understanding of the pathology of WS and develop therapeutic guidelines. Since 2009, Chiba University Hospital consecutively evaluated the WRN gene in 67 individuals throughout Japan who had requested genetic testing. A literature search was also conducted for case reports on Japanese WS reported since 1997.
  
  
  RESULTS
  A definitive diagnosis of WS was confirmed genetically in 50 of 67 participants. Through the literature search, 16 individuals diagnosed genetically with WS were identified. Of these 66 individuals with WS, 42 were homozygous for a WRN mutation, and 21 were compound heterozygotes. One novel mutant allele was identified in an individual with the compound heterozygous genotype. The proportion of compound heterozygotes (31.8%) was significantly greater than reported previously (14.2%), indicating that the incidence of consanguineous marriage of parents has decreased.
  
  
  CONCLUSIONS
  The increased frequency of individuals with WS with the compound heterozygous genotype is a recent trend in Japan. A long-term follow-up study on WRN homozygotes and compound heterozygotes will allow the relationship between WRN genotype and clinical severity of WS to be evaluated in the future.
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamaga
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Takemoto
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Takada-Watanabe
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koizumi
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kitamoto
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Koshizaka
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maezawa
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
mesh_terms: D006579:Heterozygote; D006801:Humans; D007564:Japan; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies; D014898:Werner Syndrome / Q000453:epidemiology* / Q000235:genetics; D000071657:Werner Syndrome Helicase / Q000235:genetics*
chemical_list: C098785:WRN protein, human; D000071657:Werner Syndrome Helicase
keywords: ReqQ DNA helicase; Werner gene; Werner syndrome; gene mutation