Profile of monogenic diabetes: a Pan-India study

Abstract

Aim: To evaluate the frequency of monogenic diabetes mutations among individuals clinically suspected to have monogenic diabetes in India.

Methods: Participants (n = 774) were recruited from 65 diabetes centres across India (http://monogenicdiabetes.in/Collaborators.html). Inclusion criteria were: age at diagnosis of diabetes ≤30 years; family history of diabetes in one or both parents; BMI ≤ 30 kg/m²; and absence of ketonuria. Monogenic diabetes was diagnosed based on pathogenic/ likely pathogenic mutations as per the American College of Medical Genetics and Genomics (ACMG) and Association of Medical Pathology (AMP) guidelines.

Results: The overall prevalence of monogenic diabetes mutations was 15.5 % (120/774). Mutations in HNF1A MODY were the most frequent (n = 39,32.5 %), followed by HNF4A MODY (n = 20,16.7 %), HNF1B MODY (n = 16,13.3 %), ABCC8 MODY (n = 8,6.7 %), GCK MODY (n = 4,3.3 %), PDX1 MODY (n = 1,0.8 %), and INS MODY (n = 1,0.8 %). Syndromic forms of monogenic diabetes were identified in 31 individuals: Wolfram Syndrome (n = 15), Maternally Inherited Diabetes with Deafness (n = 12), and H syndrome (histiocytosis lymphadenopathy plus syndrome) (n = 4).

Conclusion: In this Pan India study, monogenic diabetes was confirmed in 15.5% of 774 individuals screened using predefined clinical criteria. Genetic testing in carefully phenotyped individuals with youth onset diabetes, could help to detect monogenic diabetes and offer precision treatment.

Keywords: India; MIDD; MODY; Monogenic diabetes.