Non-syndromic WFS1 mutations are not a rare cause of diabetes in Pakistan
Publication: onlinelibrary.wiley.com | Publication Date: 29 April 2025
Authors: Ibrar Rafique, Asif Mir, Natalija Popovic, Alix Vanpoperinghe, Muhammad Arif Nadeem Saqib, Asher Fawwad, Abdul Basit, Muhammad Naeem, Constantin Polychronakos, Angeliki Makri
Abstract
We examined 68 Pakistani patients with young onset diabetes and found a surprisingly high rate (4/68) of non-syndromic WFS1 diabetes, a recently described recessive condition. This frequency far exceeds the prevalence of the fully expressed syndrome, probing the effect of high consanguinity on the risk of non-syndromic WFS1 diabetes.
Introduction
Diabetes is a major threat to the health care system and its prevalence is increasing globally especially in low- and middle-income countries. Similarly, diabetes related complications i.e. blindness, nephropathy, cardiovascular disease, neuropathy, amputations significantly affect the patients’ quality of life. In Pakistan, there are 32.9 million individuals suffering from diabetes, corresponding to 26 % of the general population. The major risk factors are unhealthy diet, obesity, and sedentary life style. However, in countries with high consanguinity rates, like Pakistan where more than 50 % of marriages are reportedly between first or second cousins, previously thought to be rare recessive genetic variants may play an important role.
Wolfram syndrome (WFS) is a rare autosomal recessive disorder with early onset of diabetes, deafness, optic atrophy and neurodegeneration. WFS1 mutations are increasingly being reported as a cause of diabetes in individuals with no other manifestations of Wolfram syndrome.
Given that recessive genetic variants are encountered more frequently in populations with high consanguinity rates, we hypothesized that non-syndromic WFS1 diabetes could be the underlying genetic cause in some cases of young onset diabetes in Pakistan. The present study was designed to determine the frequency of homozygous WFS1 variants in Pakistani individuals with diabetes diagnosed at a young age. To the best of our knowledge, the prevalence of non-syndromic WFS1 diabetes has not been studied in countries with high consanguinity rate.
Ibrar Rafique, Asif Mir, Natalija Popovic, Alix Vanpoperinghe, Muhammad Arif Nadeem Saqib, Asher Fawwad, Abdul Basit, Muhammad Naeem, Constantin Polychronakos, Angeliki Makri. Non-syndromic WFS1 mutations are not a rare cause of diabetes in Pakistan. Diabetes Research and Clinical Practice. 2025; 112361. https://doi.org/10.1016/j.diabres.2025.112361 Retrieved July 20, 2025, from https://www.sciencedirect.com/science/article/abs/pii/S0168822725003754.