Published online Nov 15, 2021. doi: 10.4239/wjd.v12.i11.1957
Peer-review started: May 18, 2021
First decision: July 4, 2021
Revised: July 14, 2021
Accepted: October 27, 2021
Article in press: October 27, 2021
Published online: November 15, 2021
Processing time: 180 Days and 22.8 Hours
Monogenic forms of diabetes (MFD) are single gene disorders. Their diagnosis is challenging, and symptoms overlap with type 1 and type 2 diabetes.
To identify the genetic variants responsible for MFD in the Pakistani population and their frequencies.
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 (n = 28) for exome sequencing to identify the pathogenic variants.
A total of eight missense novel or very low-frequency variants were identified in 7 patients. Three variants were found in genes for MODY, i.e. HNF1A (c.169C>A, p.Leu57Met), KLF11 (c.401G>C, p.Gly134Ala), and HNF1B (c.1058C>T, p.Ser353Leu). Five variants were found in genes other than the 14 known MODY genes, i.e. RFX6 (c.919G>A, p.Glu307Lys), WFS1 (c.478G>A, p.Glu160Lys) and WFS1 (c.517G>A, p.Glu173Lys), RFX6 (c.1212T>A, p.His404Gln) and ZBTB20 (c.1049G>A, p.Arg350His).
The study showed wide spectrum of genetic variants potentially causing MFD in the Pakistani population. The MODY genes prevalent in European population (GCK, HNF1A, and HNF4a) 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.
Core Tip: There was a lack of data on monogenic forms of diabetes (MFD) from Pakistan, therefore this study was designed to determine the genetic variants responsible for MFD in the country. The study identified wide spectrum of genetic variants potentially causing MFD. The identification of novel variants paved the way for better understanding of genetic landscape and risk factors of MFD in the country.