Molecular Biology Reports

, Volume 41, Issue 11, pp 7499–7505 | Cite as

Significant expressivity of Wolfram syndrome: phenotypic assessment of two known and one novel mutation in the WFS1 gene in three Iranian families

  • Maryam Sobhani
  • Mohammad Amin Tabatabaiefar
  • Asadollah Rajab
  • Abdol-Mohammad Kajbafzadeh
  • Mohammad Reza Noori-Daloii


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.


Wolfram syndrome Variable expressivity Mutation Iran 



This study was supported by a grant (No. 10818) from Tehran University of Medical Sciences.

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Maryam Sobhani
    • 1
  • Mohammad Amin Tabatabaiefar
    • 2
  • Asadollah Rajab
    • 3
  • Abdol-Mohammad Kajbafzadeh
    • 4
  • Mohammad Reza Noori-Daloii
    • 1
  1. 1.Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of Genetics and Molecular Biology, School of MedicineIsfahan University of Medical SciencesIsfahanIran
  3. 3.Iranian Diabetes SocietyTehranIran
  4. 4.Department of Pediatric Urology, Pediatric Urology Research Center, Children’s Hospital Medical CenterTehran University of Medical SciencesTehranIran

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