Open AccessMENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE IN EGYPTIAN CHILDREN
Author(s) -
Nermeen Galal,
Jeannette Boutros,
Aisha Marsafy,
XiaoFei Kong,
Jacqueline Feinberg,
JeanLaurent Casanova,
Stéphanie BoissonDupuis,
Jacinta Bustamante
Publication year - 2012
Publication title -
mediterranean journal of hematology and infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.682
H-Index - 31
ISSN - 2035-3006
DOI - 10.4084/mjhid.2012.033
Subject(s) - medicine , tuberculosis , mendelian inheritance , immunology , disease , vaccination , sanger sequencing , etiology , primary immunodeficiency , mycobacterium tuberculosis , immune system , gene , mutation , genetics , biology , pathology
Background: Tuberculosis remains a major health problem in developing countries especially with the emergence of multidrug resistant strains. Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare disorder with impaired immunity against mycobacterial pathogens. Reported MSMD etiologies highlight the crucial role of the Interferon gamma /Interleukin 12 (IFN-γ/ IL-12) axis and the phagocyte respiratory burst axis. Purpose: Screen patients with possible presentations for MSMD. Methods: Patients with disseminated BCG infection following vaccination, atypical mycobacterial infections or recurrent tuberculosis infections were recruited from the Primary Immune Deficiency Clinic at Cairo University Specialized Pediatric Hospital, Egypt and immune and genetic laboratory investigations were conducted at Human Genetic of Infectious Diseases laboratory in Necker Medical School, France from 2005–2009. IFN-γ level in patient’s plasma as well as mutations in the eight previously identified MSMD-causing genes were explored. Results: Nine cases from eight (unrelated) kindreds were evaluated in detail. We detected a high level of IFN-γ in plasma in one patient. Through Sanger sequencing, a homozygous mutation in the IFNGR1 gene at position 485 corresponding to an amino acid change from serine to phenylalanine (S485F), was detected in this patient. Conclusion: We report the first identified case of MSMD among Egyptian patients, including in particular a new IFNGR1 mutation underlying IFN-γR1 deficiency. The eight remaining patients need to be explored further. These findings have implications regarding the compulsory Bacillus