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Significant Expressivity of Wolfram Syndrome: Phenotypic Assessment of Two Known and One Novel Mutation in the Wfs1 Gene in Three Iranian Families Publisher Pubmed



Sobhani M1 ; Tabatabaiefar MA2 ; Rajab A3 ; Kajbafzadeh AM4 ; Nooridaloii MR1
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Poursina Ave, 16 Azar St. Keshavarz BLVD, Tehran, 1417613151, Iran
  2. 2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Iranian Diabetes Society, Tehran, Iran
  4. 4. Department of Pediatric Urology, Pediatric Urology Research Center, Children’s Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Molecular Biology Reports Published:2014


Abstract

Wolfram syndrome also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness) is a rare neurodegenerative autosomal recessive disorder. There is evidence of variable expressivity both in patients and heterozygous carriers. In this study, we describe three Persian Wolfram syndrome families with differences in the age of onset, signs and symptoms of the disease. We clinically evaluated affected families for verifying WS clinical diagnosis. After linkage analysis via 5 STR markers, molecular analysis for WFS1 was performed by direct sequencing for patients and available family members. Three homozygous mutations were identified including c.1885 C>T, c.2205C>A both in exon 8 and c.460+1G>A in intron 4. The mutation c.2205C>A was found to be novel. We report interesting phenotype-genotype correlations: homozygous c.1885C>T and c.2205C>A variants were correlated with quite different disease severity and onset in the siblings. We report a rare case of WS with homozygous c.1885C>T who is married and has a healthy child. c.460+1G>A showed a possible partial dominant inheritance put forth by a heterozygous parent showing partial WS symptoms while her daughter displayed typical WS symptoms. Due to variable expressivity, detailed clinical examination and molecular diagnostics should be used to confirm WS and a more exact recurrence risk data. © 2014, Springer Science+Business Media Dordrecht.
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