title: Maturity-onset diabetes of the young (MODY) in Brazil: Establishment of a national registry and appraisal of available genetic and clinical data.
abstract: OBJECTIVE
  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 This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data.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  311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report.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 One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals.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.affiliation: 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.
authors.forename: Fernando M A
authors.initials: FMA
authors.lastname: Giuffrida
authors.affiliation: Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Regina S
authors.initials: RS
authors.lastname: Moises
authors.affiliation: Endocrinology Unit - Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Leticia S
authors.initials: LS
authors.lastname: Weinert
authors.affiliation: Faculdade de Medicina da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Calliari
authors.affiliation: Instituto da Criança, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Thais Della
authors.initials: TD
authors.lastname: Manna
authors.affiliation: Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Renata P
authors.initials: RP
authors.lastname: Dotto
authors.affiliation: Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Luciana F
authors.initials: LF
authors.lastname: Franco
authors.affiliation: Monogenic Diabetes Group, Genetic Endocrinology Unit and Diabetes Unit, University of Sao Paulo (USP) Medical School, Sao Paulo, Brazil.
authors.forename: Lilian A
authors.initials: LA
authors.lastname: Caetano
authors.affiliation: Monogenic Diabetes Group, Genetic Endocrinology Unit and Diabetes Unit, University of Sao Paulo (USP) Medical School, Sao Paulo, Brazil.
authors.forename: Milena G
authors.initials: MG
authors.lastname: Teles
authors.affiliation: Pediatric Endocrinology Unit, University Hospital Prof. Edgard Santos, Faculty of Medicine, Federal University of Bahia, Salvador, Brazil.
authors.forename: Renata Andrade
authors.initials: RA
authors.lastname: Lima
authors.affiliation: Pediatric Endocrinology Unit, University Hospital Prof. Edgard Santos, Faculty of Medicine, Federal University of Bahia, Salvador, Brazil.
authors.forename: Crésio
authors.initials: C
authors.lastname: Alves
authors.affiliation: Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Dib
authors.affiliation: Endocrinology Unit - Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Silveiro
authors.affiliation: Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Magnus R
authors.initials: MR
authors.lastname: Dias-da-Silva
authors.affiliation: Disciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: afreis2005@gmail.com.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Reis
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D008297:Male; D012042:Registries; D055815:Young Adult
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha
keywords: Diabetes mellitus; Glucokinase; HNF1A; MODY; Monogenic diabetes