c.376G>A mutation in WFS1 gene causes Wolfram syndrome without deafness

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• 作者：Behnam Safarpour Lima^a ; Hamid Ghaedi^b ; Narsis Daftarian^c ; Hamid Ahmadieh^c ; Javad Jamshidi^d ; Mehdi Khorrami^e ; Rezvan Noroozi^b ; Nasim Sohrabifar^b ; Farhad Assarzadegan^a ; Omid Hesami^a ; Shaghayegh Taghavi^b ; Azadeh Ahmadifard^b ; Minoo Atakhorrami^b ; Simin Rahimi-Aliabadi^b ; Neda Shahmohammadibeni^f ; Elham Alehabib^b ; Monavvar Andarva^b ; Hossein Darvish^b ; ^{darvish_mg@sbmu.ac.ir" class="auth_mail" title="E-mail the corresponding author} ; Babak Emamalizadeh^b ; ^{emamalizadeh_b@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Wolfram syndrome ; WFS1 ; Psychiatric illness ; Mutation
• 刊名：European Journal of Medical Genetics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：59
• 期：2
• 页码：65-69
• 全文大小：1012 K

文摘

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.