Identification of Variants Responsible for Monogenic Forms of Diabetes in Brazil

Frontiers in Endocrinology

Melanie Rodacki¹  Lenita Zajdenverg¹  Roberta Magalhães Tarantino¹  Juliana Rosa Ferreira de Oliveira Andrade²  Pedro Hernan Cabello²  Camila de Almeida Pereira Dias Soares³  Gabriella de Medeiros Abreu³  Ritiele Bastos de Souza³  Verônica Marques Zembrzuski³  Mário Campos Junior³  Amanda Cambraia³  Ana Carolina Proença da Fonseca⁴ 

[1] Diabetes and Nutrology Section, Internal Medicine Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Laboratory of Genetics, School of Health Science, University of Grande Rio, Rio de Janeiro, Brazil;Laboratory of Human Genetics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;

关键词: monogenic diabetes;    MODY;    mitochondrial disease;    genetic diagnosis;    rare disorders;    variants;   

DOI  :  10.3389/fendo.2022.827325

来源: DOAJ

【 摘 要 】

Monogenic forms of diabetes mellitus may affect a significant number of patients of this disease, and it is an important molecular cause to be investigated. However, studies of the genetic causes of monogenic diabetes, especially in populations with mixed ethnic backgrounds, such as the one in Brazil, are scarce. The aim of this study was to screen several genes associated with monogenic diabetes in fifty-seven Brazilian patients with recurrence of the disease in their families and thirty-four relatives. Inclusion criteria were: Age of onset ≤ 40 years old, BMI < 30 kg/m², at least two affected generations and negative anti-GAD and anti-IA2 antibodies. MODY genes HNF4A, GCK, HNF1A, HNF1B, NEUROD1, KLF11, PAX4, INS, KCNJ11, and MT-TL1 were sequenced by Sanger sequencing. We identified a total of 20 patients with variants, 13 GCK-MODY, four HNF1A-MODY, and one variant in each of the following genes, HNF4A, HNF1B and MT-TL1. Segregation analysis was performed in 13 families. Four variants were novel, two in GCK (p.(Met115Val) [c.343A>G] and p.(Asp365GlufsTer95) [c.1094_1095insGCGA]) and two in HNF1A (p.(Tyr163Ter) [c.489C>G] and p.(Val380CysfsTer39) [c.1136_1137insC]). Here we highlight the importance of screening for monogenic diabetes in admixed populations.

【 授权许可】

Unknown