title: A new mutation in WFS1 gene (C.1522-1523delTA, Y508fsX421) may be responsible for early appearance of clinical features of Wolfram syndrome and suicidal behaviour.
abstract: OBJECTIVE
  Wolfram syndrome (WS) is an autosomal recessive disorder characterized by the association of juvenile-onset diabetes mellitus and optic atrophy. It is also known by the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness).
  
  
  RESULTS
  We diagnosed Wolfram syndrome in 2 male siblings and determined a new mutation (c. 1522-1523delTA, Y508fsX421). Both affected siblings were homozygous, other family members were heterozygous. Dilated renal outflow tracts in the third decade, and neuropsychiatric disorders including bipolar disorder and neurosensorial deafness appear in the fourth decade in ordinary WS, whereas these features appeared in second decade in our patients. This mutation may be responsible for early appearance of dilated renal outflow tracts and multiple neurological abnormalities. Psychiatric disturbances such as suicide were reported at increased frequency in Wolfram patients and in heterozygous carriers. Suicidal behaviour occurred in our patients when they were yet 11 and 13 years old. Therefore, our findings may indicate that there may be a relationship between this WFS1 mutation and mood disorder such as suicidal behaviour.
  
  
  CONCLUSIONS
  We determined a new mutation (c. 1522-1523delTA, Y508fsX421) in WS1 gene in 2 siblings with Wolfram syndrome. This mutation may be responsible for early appearance of clinical features of Wolfram syndrome, and there may be a relationship between this mutation and suicidal behaviour.
authors.affiliation: Department of Neurology, School of Medicine, Dicle University, Diyarbakir, Turkey. aluclu@dicle.edu.tr
authors.forename: Mehmet Ufuk
authors.initials: MU
authors.lastname: Aluclu
authors.forename: Mithat
authors.initials: M
authors.lastname: Bahceci
authors.forename: Alpaslan
authors.initials: A
authors.lastname: Tuzcu
authors.forename: Senay
authors.initials: S
authors.lastname: Arikan
authors.forename: Deniz
authors.initials: D
authors.lastname: Gokalp
mesh_terms: D017668:Age of Onset; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D001523:Mental Disorders / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D012720:Severity of Illness Index; D013405:Suicide; D014570:Urologic Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D014929:Wolfram Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein