Dataset Information

Identification of the First PAX4-MODY Family Reported in Brazil.

ABSTRACT: Purpose:The aim of this study was to sequence the coding region of the PAX4 gene in a Brazilian cohort with clinical manifestations of monogenic diabetes. Patients and Methods:This study included 31 patients with autosomal dominant history of diabetes, age at diagnosis ?40 years, BMI <30 kg/m2, and no mutations in GCK or HNF1A, HNF4A, and HNF1B. Screening of the PAX4 coding region was performed by Sanger sequencing. In silico algorithms were used to assess the potential impact of amino acid substitutions on protein structure and function. Additionally, PAX4-MODY family members and 158 control subjects without diabetes were analyzed for the identified mutation. Results:The molecular analysis of PAX4 has detected one missense mutation, p.Arg164Gln (c.491G>A), segregating with diabetes in a large Brazilian family. The mutation was absent among the control group. The index case is a woman diagnosed at 32 years of age with polyneuropathy and treated with insulin. She did not present diabetic renal disease or retinopathy. Family members with the PAX4 p.Arg164Gln mutation have a heterogeneous clinical manifestation and treatment response, with age at diagnosis ranging from 24 years to 50 years. Conclusion:To the best of our knowledge, this is the first study to report a PAX4-MODY family in Brazil. The age of PAX4-MODY diagnosis in the Brazilian family seems to be higher than the classical criteria for MODY. Our results reinforce the importance of screening large monogenic diabetes families for the understanding of the clinical manifestations of rare forms of diabetes for the specific and personalized treatment.

SUBMITTER: Abreu GM

PROVIDER: S-EPMC7399458 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of the First PAX4-MODY Family Reported in Brazil.

Abreu Gabriella de Medeiros GM Soares Camila de Almeida Pereira Dias CAPD Tarantino Roberta Magalhães RM da Fonseca Ana Carolina Proença ACP de Souza Ritiele Bastos RB Pereira Maria de Fátima Carvalho MFC Cabello Pedro Hernan PH Rodacki Melanie M Zajdenverg Lenita L Zembrzuski Verônica Marques VM Campos Junior Mário M

Diabetes, metabolic syndrome and obesity : targets and therapy 20200724

<h4>Purpose</h4>The aim of this study was to sequence the coding region of the <i>PAX4</i> gene in a Brazilian cohort with clinical manifestations of monogenic diabetes.<h4>Patients and methods</h4>This study included 31 patients with autosomal dominant history of diabetes, age at diagnosis ≤40 years, BMI <30 kg/m<sup>2</sup>, and no mutations in <i>GCK</i> or <i>HNF1A, HNF4A</i>, and <i>HNF1B</i>. Screening of the <i>PAX4</i> coding region was performed by Sanger sequencing. In silico algorithm ...[more]

PMID: 32801813

Similar Datasets

Project description:Pax4 is a paired-domain (PD)-containing transcription factor which plays a crucial role in pancreatic beta/delta-cell development. In this study, we characterized the DNA-binding and transactivation properties of mouse Pax4. Repetitive rounds of PCR-based selection led to identification of the optimal DNA-binding sequences for the PD of Pax4. In agreement with the conservation of the optimal binding sequences among the Pax family transcription factors, Pax4 could bind to the potential binding sites for Pax6, another member of the Pax family also involved in endocrine pancreas development. The overexpression of Pax4 in HIT-T15 cells dose dependently inhibited the basal transcriptional activity as well as Pax6-induced activity. Detailed domain mapping analyses using GAL4-Pax4 chimeras revealed that the C-terminal region of Pax4 contains both activation and repression domains. The activation domain was active in the embryonic kidney-derived 293/293T cells and embryonal carcinoma-derived F9 cells, containing adenoviral E1A protein or E1A-like activity, respectively but was inactive or very weakly active in other cells including those of pancreatic beta- and alpha-cell origin. Indeed, the exogenous overexpression of type 13S E1A in heterologous cell types could convert the activation domain to an active one. On the other hand, the repression domain was active regardless of the cell type. When the repression domain was linked to the transactivation domain of a heterologous transcription factor, PDX-1, it could completely abolish the transactivation potential of PDX-1. These observations suggest a primary role of Pax4 as a transcriptional repressor whose function may involve the competitive inhibition of Pax6 function. The identification of the E1A-responsive transactivation domain, however, indicates that the function of Pax4 is subject to posttranslational regulation, providing further support for the complexity of mechanisms that regulate pancreas development.

Dataset Information

Identification of the First PAX4-MODY Family Reported in Brazil.

Publications

Identification of the First PAX4-MODY Family Reported in Brazil.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets