Maturity-onset diabetes of the young (MODY) in Brazil: Establishment of a national registry and appraisal of available genetic and clinical data

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Giuffrida, Fernando M. A. ; Moises, Regina S. ; Weinert, Leticia S. ; Calliari, Luis E. ; Della Manna, Thais ; Dotto, Renata P. ; Franco, Luciana F. ; Caetano, Lilian A. ; Teles, Milena G. ; Lima, Renata Andrade ; Alves, Cresio ; Dib, Sergio A. ; Silveiro, Sandra P. ; Dias-da-Silva, Magnus R. ; Reis, Andre F. ; G, Brazilian Monogenic Diabet Study

• Document type: Journal article
• Source: Diabetes Research and Clinical Practice; v. 123, p. 134-142, JAN 2017.
• Web of Science Citations: 5

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 This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. Methods: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report.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 One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals.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 +/- 20 years; age at diagnosis 11 +/- 8 vs 21 +/- 7 years; BMI 19 +/- 6 vs 25 +/- 6 kg/m(2); 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 15/05123-9 - Cardiovascular risk stratification in diabetic patients with MODY
• Grantee: André Fernandes Reis
• Support Opportunities: Regular Research Grants