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Wolfram syndrome in the Polish population: novel mutations and genotype–phenotype correlation
Author(s) -
Zmyslowska A.,
Borowiec M.,
Antosik K.,
Szalecki M.,
Stefanski A.,
Iwaniszewska B.,
Jedrzejczyk M.,
Pietrzak I.,
Mlynarski W.
Publication year - 2011
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2011.04102.x
Subject(s) - phenotype , genotype , genetics , correlation , medicine , biology , endocrinology , mutation , population , gene , environmental health , geometry , mathematics
Summary Objective Wolfram syndrome is a rare form of diabetes mellitus associated with optic atrophy and disorders of different organs (e.g. diabetes insipidus, hearing loss, ataxia, anaemia and many others). This syndrome is caused by recessive mutations in the wolframin gene ( WFS1 ) localized on chromosome 4p16·1. The aim of this study was to identify the causative mutations in WFS1 in a group of Polish patients with suspected Wolfram syndrome. Design Patients and Measurements: Nine patients with clinical symptoms consistent with Wolfram syndrome (at least diabetes mellitus and optic atrophy) and 22 first‐degree relatives were examined. The molecular analysis was carried out by direct sequencing of the exons, the exon–intron junctions, and the 5′ and 3′ untranslated regions of WFS1 . Results Nine different mutations in WFS1 (five of them novel) were identified in the nine patients. Six patients were homozygous for the following mutations: V412fs, S443R, W539X, V659fs. They developed diabetes at a mean age of 5·2 years. Three patients were compound‐heterozygous for the following mutations: S167fs, Q392X, Y513fs, W648X, V779G. They developed diabetes at a mean age of 6·5 years. Conclusions Mean age of diagnosis of diabetes among the Polish patients was typical for Wolfram syndrome; however, compound‐heterozygous patients were slightly older at diabetes onset.