Endocrine Abstracts

Introduction: Wolfram syndrome (WS) is a genetic disorder that affects the quality of life of very young Patients. This condition is also referred to as DIDMOAD (diabetes insipidus-diabetes mellitus-optic atrophy-deafness).characterized by non immunogenic diabetes mellitus, and a progressive atrophy of the optic nerve, which occurs generally in the first decade of life.

In order to prevent and treat this condition, a better understanding of WS pathogenesis is needed through more detailed analysis of WFS1 gene product, i.e. wolframin protein.

Material and method: Seven new cases of WS were detected and WFS1 gene exon 8 was screened for mutations by PCR amplification followed by direct sequencing. Topology prediction of the protein was performed and the selected prediction was schematically drawn with the help of TOPO2 (Johns S.J., TOPO2, transmembrane protein display software (http://www.sacs.ucsf.edu/TOPO2/).

Results and conclusion: Five mutations were found to affect wolframin in these patients. From these mutations, W588X, A684G, and E752K are novel. E717K, which is a rare mutation in other populations, was observed in all WS patients in this study, and is suggested to be further investigated to be proposed as a WS marker in the Iranian population. Positions 684 and 752 of wolframin appear to be hot spots for mutations, as other missense mutations have been reported in these positions in other populations. W588X is a novel deletion that would lead toa truncated protein after the eighth transmembrane segment, and is related to the severity of symptoms observed in the patients who bears it.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Keywords: Wolfram syndrome, wolframin, mutation, polymorphism.