Fernando M A Giuffrida1, Regina S Moises2, Leticia S Weinert3, Luis E Calliari4, Thais Della Manna5, Renata P Dotto2, Luciana F Franco2, Lilian A Caetano6, Milena G Teles6, Renata Andrade Lima7, Crésio Alves7, Sergio A Dib2, Sandra P Silveiro3, Magnus R Dias-da-Silva2, Andre F Reis8. 1. Universidade do Estado da Bahia (UNEB), Salvador, Brazil; Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: fernando.giuffrida@me.com. 2. Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 3. Endocrinology Unit - Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. 4. Faculdade de Medicina da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. 5. Instituto da Criança, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. 6. Monogenic Diabetes Group, Genetic Endocrinology Unit and Diabetes Unit, University of Sao Paulo (USP) Medical School, Sao Paulo, Brazil. 7. Pediatric Endocrinology Unit, University Hospital Prof. Edgard Santos, Faculty of Medicine, Federal University of Bahia, Salvador, Brazil. 8. Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: afreis2005@gmail.com.
Abstract
AIMS: Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase (GCK) and hepatocyte nuclear factor-1 homeobox A (HNF1A). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. METHODS: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report. RESULTS: 72 individuals had GCK mutations, 9 described in Brazilian individuals for the first time. One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals. Comparisons of GCK probands vs HNF1A: age 16±11 vs 35±20years; age at diagnosis 11±8 vs 21±7years; BMI 19±6 vs 25±6kg/m2; sulfonylurea users 5 vs 83%; insulin users 5 vs 17%; presence of arterial hypertension 0 vs. 33%, all p<0.05. No differences were observed in lipids and C-peptide. CONCLUSIONS: Most MODY cases in Brazil are due to GCK mutations. In agreement with other studied populations, novel mutations are common. Only 14% of patients with familial diabetes carry a HNF1A mutation. Diagnosis of other rare forms of MODY is still a challenge in Brazilian population, as well as adequate strategies to screen individuals for molecular diagnosis.
AIMS: Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase (GCK) and hepatocyte nuclear factor-1 homeobox A (HNF1A). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. METHODS: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report. RESULTS: 72 individuals had GCK mutations, 9 described in Brazilian individuals for the first time. One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals. Comparisons of GCK probands vs HNF1A: age 16±11 vs 35±20years; age at diagnosis 11±8 vs 21±7years; BMI 19±6 vs 25±6kg/m2; sulfonylurea users 5 vs 83%; insulin users 5 vs 17%; presence of arterial hypertension 0 vs. 33%, all p<0.05. No differences were observed in lipids and C-peptide. CONCLUSIONS: Most MODY cases in Brazil are due to GCK mutations. In agreement with other studied populations, novel mutations are common. Only 14% of patients with familial diabetes carry a HNF1A mutation. Diagnosis of other rare forms of MODY is still a challenge in Brazilian population, as well as adequate strategies to screen individuals for molecular diagnosis.
Authors: Gabriella de Medeiros Abreu; Roberta Magalhães Tarantino; Ana Carolina Proença da Fonseca; Juliana Rosa Ferreira de Oliveira Andrade; Ritiele Bastos de Souza; Camila de Almeida Pereira Dias Soares; Amanda Cambraia; Pedro Hernan Cabello; Melanie Rodacki; Lenita Zajdenverg; Verônica Marques Zembrzuski; Mário Campos Junior Journal: Front Endocrinol (Lausanne) Date: 2022-05-03 Impact factor: 6.055
Authors: Shu-Qin Lei; Jie-Ying Wang; Rong-Min Li; Jie Chang; Zhen Li; Li Ren; Yan-Mei Sang Journal: Am J Transl Res Date: 2020-10-15 Impact factor: 4.060
Authors: Lucas S de Santana; Lilian A Caetano; Aline D Costa-Riquetto; Pedro C Franco; Renata P Dotto; André F Reis; Letícia S Weinert; Sandra P Silveiro; Marcio F Vendramini; Flaviene A do Prado; Giovanna C P Abrahão; Ana Gregória F P de Almeida; Maria da G Rodrigues Tavares; Wagner Rodrigo B Gonçalves; Augusto C Santomauro Junior; Bruno Halpern; Alexander A L Jorge; Marcia Nery; Milena G Teles Journal: Mol Genet Genomic Med Date: 2019-10-08 Impact factor: 2.183