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Title: Maturity-Onset Diabetes of the Young (MODY) in Portugal: Novel GCK, HNFA1 and HNFA4 Mutations
Authors: Alvelos, Maria I.
Gonçalves, Catarina I.
Coutinho, Eduarda 
Almeida, Joana T.
Bastos, Margarida 
Sampaio, Maria L.
Melo, Miguel 
Martins, Sofia
Dinis, Isabel
Mirante, Alice
Gomes, Leonor 
Saraiva, Joana
Pereira, Bernardo D.
Gama-de-Sousa, Susana
Moreno, Carolina 
Guelho, Daniela
Martins, Diana 
Baptista, Carla
Barros, Luisa 
Ventura, Mara
Gomes, Maria M.
Lemos, Manuel C. 
Keywords: diabetes; MODY; genetics; mutation
Issue Date: 20-Jan-2020
Publisher: MDPI
Serial title, monograph or event: Journal of Clinical Medicine
Volume: 9
Issue: 1
Abstract: Maturity-onset diabetes of the young (MODY) is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. The most frequent subtypes are due to mutations of the GCK (MODY 2), HNF1A (MODY 3), and HNF4A (MODY 1) genes. We undertook the first multicenter genetic study of MODY in the Portuguese population. The GCK, HNF1A, and HNF4A genes were sequenced in 46 unrelated patients that had at least two of the three classical clinical criteria for MODY (age at diagnosis, family history, and clinical presentation). The functional consequences of the mutations were predicted by bioinformatics analysis. Mutations were identified in 23 (50%) families. Twelve families had mutations in the GCK gene, eight in the HNF1A gene, and three in the HNF4A gene. These included seven novel mutations (GCK c.494T>C, GCK c.563C>G, HNF1A c.1623G>A, HNF1A c.1729C>G, HNF4A c.68delG, HNF4A c.422G>C, HNF4A c.602A>C). Mutation-positive patients were younger at the time of diagnosis when compared to mutation-negative patients (14.3 vs. 23.0 years, p = 0.011). This study further expands the spectrum of known mutations associated with MODY, and may contribute to a better understanding of this type of diabetes and a more personalized clinical management of affected individuals.
ISSN: 2077-0383
DOI: 10.3390/jcm9010288
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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