title: c.376G>A mutation in WFS1 gene causes Wolfram syndrome without deafness.
abstract: Wolfram syndrome is one of the rare autosomal recessive, progressive, neurodegenerative disorders, characterized by diabetes mellitus and optic atrophy. Several other features are observed in patients including deafness, ataxia, and peripheral neuropathy. A gene called WFS1 is identified on chromosome 4p, responsible for Wolfram syndrome. We investigated a family consisted of parents and 8 children, which 5 of them have been diagnosed for Wolfram syndrome. WFS1 gene in all family members was sequenced for causative mutations. A mutation (c.376G>A, p.A126T) was found in all affected members in homozygous state and in both parents in heterozygous state. The bioinformatics analysis showed the deleterious effects of this nucleotide change on the structure and function of the protein product. As all of the patients in the family showed the homozygote mutation, and parents were both heterozygote, this mutation is probably the cause of the disease. We identified this mutation in homozygous state for the first time as Wolfram syndrome causation. We also showed that this mutation probably doesn't cause deafness in affected individuals.
authors.affiliation: Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Behnam
authors.initials: B
authors.lastname: Safarpour Lima
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ghaedi
authors.affiliation: Ophthalmic Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Narsis
authors.initials: N
authors.lastname: Daftarian
authors.affiliation: Ophthalmic Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ahmadieh
authors.affiliation: Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Jamshidi
authors.affiliation: Department of Medical Genetics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khorrami
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Rezvan
authors.initials: R
authors.lastname: Noroozi
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Nasim
authors.initials: N
authors.lastname: Sohrabifar
authors.affiliation: Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Assarzadegan
authors.affiliation: Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Hesami
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Shaghayegh
authors.initials: S
authors.lastname: Taghavi
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Ahmadifard
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Minoo
authors.initials: M
authors.lastname: Atakhorrami
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Simin
authors.initials: S
authors.lastname: Rahimi-Aliabadi
authors.affiliation: Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran.
authors.forename: Neda
authors.initials: N
authors.lastname: Shahmohammadibeni
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Alehabib
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Monavvar
authors.initials: M
authors.lastname: Andarva
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: darvish_mg@sbmu.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Darvish
authors.affiliation: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: emamalizadeh_b@yahoo.com.
authors.forename: Babak
authors.initials: B
authors.lastname: Emamalizadeh
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation; D014929:Wolfram Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein
keywords: Mutation; Psychiatric illness; WFS1; Wolfram syndrome