AUTHOR=Abreu Gabriella de Medeiros , Tarantino Roberta Magalhães , da Fonseca Ana Carolina Proença , Andrade Juliana Rosa Ferreira de Oliveira , de Souza Ritiele Bastos , Soares Camila de Almeida Pereira Dias , Cambraia Amanda , Cabello Pedro Hernan , Rodacki Melanie , Zajdenverg Lenita , Zembrzuski Verônica Marques , Campos Junior Mário 

TITLE=Identification of Variants Responsible for Monogenic Forms of Diabetes in Brazil

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.827325

DOI=10.3389/fendo.2022.827325

ISSN=1664-2392

ABSTRACT=<p>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 &lt; 30 kg/m², at least two affected generations and negative anti-GAD and anti-IA2 antibodies. MODY genes <italic>HNF4A</italic>, <italic>GCK</italic>, <italic>HNF1A</italic>, <italic>HNF1B</italic>, <italic>NEUROD1</italic>, <italic>KLF11</italic>, <italic>PAX4</italic>, <italic>INS</italic>, <italic>KCNJ11</italic>, and <italic>MT-TL1</italic> 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, <italic>HNF4A</italic>, <italic>HNF1B</italic> and <italic>MT-TL1</italic>. Segregation analysis was performed in 13 families. Four variants were novel, two in <italic>GCK</italic> (p.(Met115Val) [c.343A&gt;G] and p.(Asp365GlufsTer95) [c.1094_1095insGCGA]) and two in <italic>HNF1A</italic> (p.(Tyr163Ter) [c.489C&gt;G] and p.(Val380CysfsTer39) [c.1136_1137insC]). Here we highlight the importance of screening for monogenic diabetes in admixed populations.</p>