Comprehensive genetic screening reveals wide spectrum of genetic variants in monogenic forms of diabetes among Pakistani population.

Background: Monogenic forms of diabetes (MFD) are single gene disorders. Their diagnosis is challenging, and symptoms overlap with type 1 and type 2 diabetes.

Aim: To identify the genetic variants responsible for MFD in the Pakistani population and their frequencies.

Methods: A total of 184 patients suspected of having MFD were enrolled. The inclusion criterion was diabetes with onset below 25 years of age. Brief demographic and clinical information were taken from the participants. The maturity-onset diabetes of the young (MODY) probability score was calculated, and glutamate decarboxylase ELISA was performed. Antibody negative patients and features resembling MODY were selected ( = 28) for exome sequencing to identify the pathogenic variants.

Results: A total of eight missense novel or very low-frequency variants were identified in 7 patients. Three variants were found in genes for MODY, (c.169C>A, p.Leu57Met), (c.401G>C, p.Gly134Ala), and (c.1058C>T, p.Ser353Leu). Five variants were found in genes other than the 14 known MODY genes, (c.919G>A, p.Glu307Lys), (c.478G>A, p.Glu160Lys) and (c.517G>A, p.Glu173Lys), (c.1212T>A, p.His404Gln) and (c.1049G>A, p.Arg350His).

Conclusion: The study showed wide spectrum of genetic variants potentially causing MFD in the Pakistani population. The MODY genes prevalent in European population () were not found to be common in our population. Identification of novel variants will further help to understand the role of different genes causing the pathogenicity in MODY patient and their proper management and diagnosis.