title: The WFS1 (Wolfram syndrome 1) is not a major susceptibility gene for the development of psychiatric disorders.
abstract: BACKGROUND
  Wolfram syndrome is a neurodegenerative disorder that is inherited in an autosomal recessive mode and characterized by the presence of diabetes mellitus and optic atrophy. Patients and heterozygote carriers are at an increased risk of suffering psychiatric disorders. Mutations in the Wolfram gene (WFS1 ) (4p16.1) are responsible for the development of the disease, and mRNA and protein expression of WFS1 have recently been found in areas of the rat brain that can be related to the psychiatric symptoms.
  
  
  OBJECTIVE
  To test the hypothesis that WFS1 mutations in heterozygote carriers or other variants of WFS1 can predispose to mental illness.
  
  
  METHODS
  Stage 1: Exons 2, 4 and 8 of that harbour mutations in Spanish Wolfram syndrome families were examined by Single Strand Conformation Polymorphism and sequencing analysis in 43 patients with affective disorder to identify variants and mutations. Stage 2: two variants identified in stage 1 were analysed in 152 psychiatric patients (118 schizophrenia and 34 affective disorder) and 177 control subjects.
  
  
  RESULTS
  Six variants (I333V Ile-->Val, F341, N500, R708, K774, K811) and a WFS1 mutation (R818C, Arg-->Cys) were found in the 43 patients analysed in stage 1 of the study. In stage 2, the R818C mutation was not found in the group of psychiatric patients but it was present in one control subject. The association study conducted with the I333V variant did not find significant differences in allele or genotype frequencies between patients and control subjects.
  
  
  CONCLUSIONS
  Our results suggest that WFS1 is not a major susceptibility gene for the development of psychiatric disorders in our population.
authors.affiliation: Departament de Formació i Investigació, Hospital Psiquiàtric Universitari Institut Pere Mata, Ctra. de l'Institut Pere Mata s/n, Reus, Spain. lmartorell@grupsagessa.com
authors.forename: Lourdes
authors.initials: L
authors.lastname: Martorell
authors.forename: Montse Gómez
authors.initials: MG
authors.lastname: Zaera
authors.forename: Joaquín
authors.initials: J
authors.lastname: Valero
authors.forename: Dolors
authors.initials: D
authors.lastname: Serrano
authors.forename: Lídia
authors.initials: L
authors.lastname: Figuera
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.forename: Antonio
authors.initials: A
authors.lastname: Labad
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella
authors.forename: Virginia
authors.initials: V
authors.lastname: Nunes
mesh_terms: D019943:Amino Acid Substitution; D004198:Disease Susceptibility; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D019083:Mediterranean Region; D008565:Membrane Proteins / Q000235:genetics*; D019964:Mood Disorders / Q000235:genetics*; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics*; D013030:Spain; D044465:White People; D014929:Wolfram Syndrome / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; C114987:wolframin protein