Profile of monogenic diabetes: a Pan-India study.

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.