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Nermeen Galal
Jeannette Boutros
Aisha Marsafy
Xiao-Fei Kong
Jacqueline Feinberg
Jean-Laurent Casanova
Stéphanie Boisson-Dupuis
Jacinta Bustamante


Tuberculosis, Interferon gamma, BCG, Consanguinity


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-g/ 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-g 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-g 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 cases of MSMD among Egyptian patients, including in particular a new IFNGR1 mutation underlying IFN-gR1 deficiency. The eight remaining patients need to be explored further. These findings have implications regarding the compulsory Bacillus Calmette Guerin vaccination policy in Egypt, especially given the high consanguinity rate.

Keywords: Interferon gamma axis, mycobacterium tuberculosis, BCG, consanguinity


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