Genetic and functional evaluation of novel genes associated with Mendelian susceptibility to mycobacterial infections

• Grant number: 12/11757-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: September 20, 2012
• End date: September 19, 2013
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Antonio Condino Neto
• Grantee: Edgar Borges de Oliveira Junior
• Supervisor: Jean-Laurent Casanova
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Université Paris Descartes - Paris 5, France
• Associated to the scholarship: 10/51336-0 - New molecular genetic defects involved in Mendelian susceptibility to mycobacterial infections, BP.PD

Abstract

Tuberculosis is an infectious disease caused by mycobacterium tuberculosis complex. The main pathogen is Mycobacterium tuberculosis. Approximately 8 million new cases and 2 million deaths are reported each year. Through the study of the susceptibility Mendelian diseases caused by mycobacteria (MSMD), mutations were identified in six genes related to the operation axis interleukin 12 (IL-12) and interferon-gamma (IFN-³), some of which lead to defects the "burst" oxidative similar to those found in patients with chronic granulomatous disease (CGD). We obtained preliminary results involving 10 patients with mycobacterial disease associated with hematological disorders, in which we will initiate investigation of mutations in the GATA2 gene, an excellent candidate for possible mutations, and through the sequencing of exoma also seek other genes that may be related to the NADPH oxidase and/shaft system or IL-12/IFN-gama. Our future prospects are based on further investigation of these patients, among others, searching for new genes or new mutations involved in susceptibility to mycobacterial infections by family segregation analysis and/or analysis of exoma stage during the Laboratory of Human Genetics, Hospital Necker, Paris, France. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CONTI, FRANCESCA; OSWALDO LUGO-REYES, SAUL; BLANCAS GALICIA, LIZBETH; HE, JIANXIN; AKSU, GUZIDE; DE OLIVEIRA, JR., EDGAR BORGES; DESWARTE, CAROLINE; HUBEAU, MARJORIE; KARACA, NESLIHAN; DE SUREMAIN, MAYLIS; et al. Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases. Journal of Allergy and Clinical Immunology, v. 138, n. 1, p. 241+, JUL 2016. (12/11757-2, 10/51814-0)

OLEAGA-QUINTAS, CARMEN; DE OLIVEIRA-JUNIOR, EDGAR BORGES; ROSAIN, JEREMIE; RAPAPORT, FRANCK; DESWARTE, CAROLINE; GUERIN, ANTOINE; SAJJATH, SAIRAJ MUNAVAR; ZHOU, YU JERRY; MAROT, STEPHANE; LOZANO, CLAIRE; et al. Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance. JOURNAL OF CLINICAL IMMUNOLOGY, v. 41, n. 3, JAN 2021. (12/11757-2, 10/51814-0)