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Licensed Unlicensed Requires Authentication Published by De Gruyter May 29, 2019

Wolcott-Rallison syndrome in Iran: a common cause of neonatal diabetes

Samaneh Noroozi Asl, Rahim Vakili, Saba Vakili, Fahimeh Soheilipour, Mahin Hashemipour, Sara Ghahramani, Elisa De Franco and Hanieh Yaghootkar



Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by neonatal/early-onset non-autoimmune insulin-dependent diabetes, multiple epiphyseal dysphasia and growth retardation. It is caused by mutations in the gene encoding eukaryotic translation initiation factor 2α kinase 3 (EIF2AK3). We aimed to study the clinical characteristics and frequency of the disease in the Iranian population.


We recruited 42 patients who referred to the endocrine and metabolism clinic at Mashhad Imam Reza Hospital with neonatal diabetes. Molecular screening of KCNJ11, INS, ABCC8 and EIF2AK3 was performed at the Exeter Molecular Genetics Laboratory, UK. We calculated the frequency of the disease in 124 patients referred from Iran to the Exeter Molecular Genetics Laboratory for genetic screening and compared it to other countries worldwide.


We identified seven patients as having Wolcott-Rallison syndrome. Genetic testing confirmed the clinical diagnosis and indicated five novel mutations. Only two patients developed clinical features of the syndrome by 6 months of age. Of all 124 cases of Iranian neonatal diabetes referred to the Exeter Molecular Genetics Laboratory for genetic screening, 28 patients (22.58%) had a recessive mutation in EIF2AK3.


The results of this study raises awareness of the condition and provides further accurate data on the genetic and clinical presentation of Wolcott-Rallison syndrome in the Iranian population. Our study highlights the importance of genetic testing in patients from consanguineous families with diabetes diagnosed within the first 6 months of life.


This work was supported by the Wellcome Trust [108101/Z/15/Z]. H.Y. was funded by Diabetes UK RD Lawrence fellowship (grant: 17/0005594). We thank all the families and their referring clinicians. We thank Dr. Samuel E Jones, University of Exeter, for proofreading this manuscript.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2018-10-09
Accepted: 2019-04-17
Published Online: 2019-05-29
Published in Print: 2019-06-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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