MODY accounts for 1-2% of all diabetes cases. There are more than 20 genes linked with MODY. Unfortunately, ca. 90% of MODY cases are misdiagnosed as type 1 or type 2 diabetes. A proper diagnosis of the type of diabetes is crucial for the use of a tailored treatment. Next-generation sequencing (NGS) enables simultaneous testing of a set of genes responsible for MODY. However, this method is still not reimbursed in many countries and patients' selection for testing should be performed preciously. In 2012, an easy-to-use tool have been developed in Exeter, UK, to support the identification of cases appropriate for genetic testing in the British population. The aim of the study was to assess the utility of MODY Probability Calculator (MODY-PC) in Polish patients.
We have performed a retrospective analysis of 152 probands who were qualified for genetic testing between 2006 and 2018. Patients were recruited for MODY testing according to the classical clinical guidelines that include early age of diagnosis (≤35 years) and a positive, multigenerational family history. If Sanger sequencing for most likely gene was negative, NGS of a set of 28 genes was performed. MODY Probability was calculated on the website: www.diabetesgenes.org.
The study group consists of 64 GCK-, 37 HNF1A-MODY and 51 NGS-negative patients. The mean positive predictive value (PPV) was 66,6±17,7, 46,7±27,3 and 53,3±26,3% for GCK-, HNF-MODY and NGS-negative, respectively. The optimal statistical cut-off point to distinguish between MODY and NGS-negative patients was 58% (AUC: 0,568, 95% CI: 0,47-0,67). In such settings, in the analyzed group sensitivity and specificity was 64,4% and 49,0%, respectively. When using cut-off point of PPV for genetic testing of 25% sensitivity was 87,1% and specificity 17,6%.
In the analyzed group of probands that were qualified for genetic testing based on clinical features the use of MODY-PC would not substantially improve patients' selection process for genetic testing. Further improvement of MODY-PC is desirable.
J. Hohendorff: Other Relationship; Self; Abbott, Ascensia Diabetes Care, Novo Nordisk A/S, Sanofi-Aventis. B. Zapala: None. I. Solecka: None. D. Ucieklak: None. A. Ludwig-Slomczynska: None. B. Matejko: Research Support; Self; Roche Diabetes Care. Other Relationship; Self; Ascensia Diabetes Care. S. Mrozinska: Other Relationship; Self; EGIS Polska. M. Malecki: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Bioton, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. Speaker's Bureau; Self; Merck & Co., Inc. M. Szopa: None.
Polish Diabetes Association (2016 to M.S.); Jagiellonian University Medical College (K/ZDS/006219 to M.S.), (K/ZDS/005596 to M.M.)