Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder that represents a likely source of childhood diabetes especially among countries in the consanguinity belt. The main responsible gene is WFS1 for which over one hundred mutations have been reported from different ethnic groups. The aim of this study was to identify the molecular etiology of WS and to perform a possible genotype-phenotype correlation in Iranian kindred. An Iranian family with two patients was clinically studied and WS was suspected. Genetic linkage analysis via 5 STR markers was carried out. For identification of mutations, DNA sequencing of WFS1 including all the exons, exon-intron boundaries and the promoter was performed. Linkage analysis indicated linkage to the WFS1 region. After DNA sequencing of WFS1, one novel pathogenic mutation, which causes frameshift alteration c.2177_2178insTCTTC (or c.2173_2177dupTCTTC) in exon eight, was found. The genotype-phenotype correlation analysis suggests that the presence of the homozygous mutation may be associated with early onset of disease symptoms. This study stresses the necessity of considering the molecular analysis of WFS1 in childhood diabetes with some symptoms of WS.
Keywords: BLAST; Basic Local Alignment Search Tool; DI; DI-DM-OA-D; DM; DNA; Dup; EDTA; FVC; Genetic linkage analysis; Iran; LOD; NCBI; National Center for Biotechnology Information; Novel mutation; OA; PAGE; PCR; SLINK; STR; VCUG; WFS1; WS; Wolfram syndrome; Wolfram syndrome 1 gene; aa; amino acid; dNTP; ddH2O; deoxyribonucleic acid; deoxyribonucleotide triphosphate; diabetes insipidus; diabetes insipidus, diabetes mellitus, optic atrophy and deafness; diabetes mellitus; double-distilled dihydrogen monoxide/water; duplication; ethylenediaminetetraacetic acid; frequency volume chart; logarithm of odds; optic atrophy; polyacrylamide gel electrophoresis; polymerase chain reaction; short tandem repeats; simulation of linkage; voiding cystourethrogram.
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