Genetic characterization of suspected MODY patients in Pakistan by next generation sequencing—a pilot study.

Background: Maturity onset diabetes of the young (MODY) is the genetic form of diabetes inherited in autosomal dominant pattern. The diagnosis of MODY is challenging and confirmed by genetic testing. The objective of this study was to investigate MODY in Pakistani patients using next-generation sequencing. Methods: The next-generation sequencing was performed to know the cause of disease in 07 patients phenotypically suspected for MODY from Pakistan. These patients were selected based on the high probability score through MODY probability calculator. Only those genetic variants were retained which were having low frequency as per available data bases and their potential effects on protein as assessed by bioinformatics prediction tools. Results: Four heterozygous variants were found among patients. This includes mutation in HNF1a gene (c.526+1G>A) that is already reported for causative for MODY type 3 which is most prevalent among all MODY sub-types. Other variants were identified in GCK (c.-45G>A), KLF11 (c.*96dupA), and CEL (c.1235C>T). Conclusion: This study was the first in Pakistan to investigate the MODY using next-generation sequencing for clinical applications. There is huge public health burden of diabetes in the country. The study identified mutation in one known MODY gene. More extensive studies involving large sample size are required in future. [ABSTRACT FROM AUTHOR]