The Genetic Profile of Maturity Onset Diabetes of the Young in Sri Lanka using Next Generation Sequencing BackgroundMaturity Onset Diabetes of Young (MODY) is a monogenic type of diabetes with clinical, metabolic and genetic heterogenecity which is characterized by young onset (< 25 years) diabetes, early onset diabetes in family members, autosomal dominant inheritance and non-insulin dependence. Definitive diagnosis of MODY is vital to decide on personalized therapy and for family screening, which need genetic categorization. The estimated prevalence of MODY is about 0.8-2% [1,2,3] among diabetes patients which make it imperative to develop specific screening criteria to pick up those who are having highest pretest probability to be referred for genetic screening which is a technically demanding and expensive investigation. AimsThe objectives of this study are to develop specific clinical and biochemical screening criteria for MODY to refer for MODY genetic categorization. And then to utilize a Next Generation Sequencing (NGS) based strategy for MODY gene mutations analysis in a similarly selected cohort of patients for establishment of genetic mutations of MODY types in Sri Lankan population and family screening of index cases to bring about a genetic characterization to MODY patients in Sri Lanka MethodsThis is a cross sectional analytical study among patients with diabetes referred to the diabetic clinic National Hospital of Sri Lanka. The specific screening criteria for MODY which were used as inclusion criteria were: Onset of diabetes before 40 years of age, presence of 2 or 3 generation family history of diabetes, absence of beta cell immunity (Negative GAD antibody), no history of diabetes ketoacidosis, evidence of endogenous insulin production (detection of measurable C peptide in the presence of hyperglycemia and low Insulin requirement (A was classified as pathogenic variant according to American College of Medical Genetics and Genomics (ACMG) 2015 classification. ABCC8 c.2401G>T, HNF1A c.1135C>T and PDX1 c.98C>A were classified as likely pathogenic and KLF11 c.1120G>A as variant with uncertain significance. DiscussionThis confirms that the specific criteria we have used to select patients for MODY screening has yielded a prevalence value of 18% and it can be used as future screening model. Few of the PDX1 gene variants based on the ExAC has been suggested that these variants could be benign. However, these variants are consistently very rare with a MAF