title: Identification of four novel mutations of the WFS1 gene in Iranian Wolfram syndrome pedigrees.
abstract: OBJECTIVE
  Wolfram syndrome is a rare neurodegenerative disorder with an autosomal recessive pattern of inheritance characterized by various clinical manifestations. The related gene, WFS1, encodes a transmembrane glycoprotein, named wolframin. Genetic analyses demonstrated that mutations in this gene are associated with WS type 1. Our aim in this study was to sequence WFS1 coding region in Iranian Wolfram syndrome pedigrees.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood of 12 WS patients and their healthy parents. Exons 2-8 and the exon-intron junctions of WFS1 were sequenced. DNA sequences were compared to the reference using Sequencher software.
  
  
  RESULTS
  Molecular analysis of WFS1 revealed six different mutations. Four novel and two previously reported mutations were identified. One novel mutation, c.1379_1381del, is predicted to produce an aberrant protein. A second novel mutation, c.1384G > T, encodes a truncated protein. Novel mutation, c.1097-1107dup (11 bp), causes a frameshift which results in a premature stop codon. We screened for the novel missense mutation, c.1010C > T, in 100 control alleles. This mutation was not found in any of the healthy controls.
  
  
  CONCLUSIONS
  Our study increased the spectrum of WFS1 mutations and supported the role of WFS1 in susceptibility to WS. We hope that these findings open new horizons to future molecular investigations which may help to prevent and treat this devastating disease.
authors.affiliation: Medical Genetic Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Human Genetics Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Martha
authors.initials: M
authors.lastname: Ghahraman
authors.affiliation: Medical Genetic Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Human Genetics Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Abbaszadegan
authors.affiliation: Medical Genetic Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Pediatric Endocrinology and Metabolism, Imam Reza Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Rahim
authors.initials: R
authors.lastname: Vakili
authors.affiliation: Medical Genetic Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Sousan
authors.initials: S
authors.lastname: Hosseini
authors.affiliation: Medical Genetic Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Human Genetics Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Fardi Golyan
authors.affiliation: Department of Pediatric Endocrinology and Metabolism, Imam Reza Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. ghaemiN@mums.ac.ir.
authors.forename: Nosrat
authors.initials: N
authors.lastname: Ghaemi
authors.affiliation: Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Forghanifard
mesh_terms: D000328:Adult; D005260:Female; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D014929:Wolfram Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein
keywords: Iranian pedigrees; Novel mutations; WFS1 gene; Wolfram syndrome