학술논문
Maturity-onset diabetes of the young in a large Portuguese cohort
Document Type
Original Paper
Author
Santos Monteiro, Sílvia; da Silva Santos, Tiago; Fonseca, Liliana; Assunção, Guilherme; Lopes, Ana M.; Duarte, Diana B.; Soares, Ana Rita; Laranjeira, Francisco; Ribeiro, Isaura; Pinto, Eugénia; Rocha, Sónia; Barbosa Gouveia, Sofia; Vazquez-Mosquera, María Eugenia; Oliveira, Maria João; Borges, Teresa; Cardoso, Maria Helena
Source
Acta Diabetologica. 60(1):83-91
Subject
Language
English
ISSN
1432-5233
Abstract
Aims: Monogenic forms of diabetes that develop with autosomal dominant inheritance are classically aggregated in the Maturity-Onset Diabetes of the Young (MODY) categories. Despite increasing awareness, its true prevalence remains largely underestimated. We describe a Portuguese cohort of individuals with suspected monogenic diabetes who were genetically evaluated for MODY-causing genes.Methods: This single-center retrospective cohort study enrolled patients with positive genetic testing for MODY between 2015 and 2021. Automatic sequencing and, in case of initial negative results, next-generation sequencing were performed. Their clinical and molecular characteristics were described.Results: Eighty individuals were included, 55 with likely pathogenic/pathogenic variants in one of the MODY genes and 25 MODY-positive family members, identified by cascade genetic testing. The median age at diabetes diagnosis was 23 years, with a median HbA1c of 6.5%. The most frequently mutated genes were identified in HNF1A (40%), GCK (34%) and HNF4A (13%), followed by PDX1, HNF1B, INS, KCNJ11 and APPL1. Thirty-six unique variants were found (29 missense and 7 frameshift variants), of which ten (28%) were novel.Conclusions: Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of its subtypes, leading to more personalized treatment and follow-up strategies.