Targeted next-generation sequencing for maturity onset diabetes of the young (MODY) in a South Indian cohort of type 1 diabetes mellitus patients with preserved C-peptide.

Objective: MODY (maturity onset diabetes of the young) is a rare, monogenic, autosomal dominant form of diabetes occurring in young (< 25 years) individuals. It has a wide phenotypic variability and can be misdiagnosed as type 1 diabetes mellitus (T1DM). Appropriate detection of MODY has therapeutic and genetic implications. This study aimed to detect MODY among long standing, clinically diagnosed T1DM patients with preserved C-peptide levels. Methods: This was a hospital-based cross-sectional study from central South India which included 100 clinically diagnosed T1DM patients (according to ADA criteria), with a duration of > 3 years. MODY probability score, urinary C-peptide to creatinine ratio (UCPCR), and relevant biochemical investigations were performed. Targeted next-generation sequencing (NGS) for MODY-related genes (13 genes) was done for individuals with UCPCR > 0.2. Results: A UCPCR value of > 0.2 (suggestive of preserved endogenous insulin secretion) was observed in eight individuals. The mean HbA1c values were lower, and the MODY probability score was higher in individuals with preserved endogenous insulin (8.07% vs 9.53% and 2.8% vs 1.5%; p-value: 0.005 and 0.004 respectively). One of the eight individuals (12.5%) had a non-pathogenic gene variant in KLF11. Conclusion: In a South Indian cohort of T1DM with preserved C-peptide, we could not find any case of MODY through targeted NGS. UCPCR can be used as a screening tool to identify cases needing genetic testing for MODY. Larger studies utilizing whole exome sequencing should be conducted to know the actual prevalence of MODY among T1DM. [ABSTRACT FROM AUTHOR]