A novel X-linked recessive form of Mendelian susceptibility to mycobaterial disease. Issue 2 (9th February 2007)

• Record Type: Journal Article
• Authors: Bustamante, Jacinta; Picard, Capucine; Fieschi, Claire; Filipe-Santos, Orchidée; Feinberg, Jacqueline; Perronne, Christian; Chapgier, Ariane; de Beaucoudrey, Ludovic; Vogt, Guillaume; Sanlaville, Damien; Lemainque, Arnaud; Emile, Jean-François; Abel, Laurent; Casanova, Jean-Laurent
• Is Part Of: Journal of medical genetics. Volume 44:Issue 2(2007)
• Page Start: e65
• Page End: e65
• Publication Date: 2007-02-09
• Subjects: BCG, bacille Calmette–Guérin -- EBV, Epstein–Barr virus -- IFN, interferon -- LOD, logarithm of odds -- LZD, leucine zipper domain -- MSMD, Mendelian susceptibility to mycobacterial disease -- NEMO, nuclear factor-κB essential modulator -- PBMC, peripheral blood mononuclear cells -- Stat 1, signal transducer and activator of transcription 1 -- XR-MSMD, X-linked recessive MSMD; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2006.043406
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Mendelian susceptibility to mycobacterial disease (MSMD) is associated with infection caused by weakly virulent mycobacteria in otherwise healthy people. Causal germline mutations in five autosomal genes ( IFNGR1, IFNGR2, STAT1, IL12RB1, IL12B ) and one X-linked ( NEMO ) gene have been described. The gene products are physiologically related, as they are involved in interleukin 12/23-dependent, interferon γ-mediated immunity. However, no genetic aetiology has yet been identified for about half the patients with MSMD. Methods: A large kindred was studied, including four male maternal relatives with recurrent mycobacterial disease, suggesting X-linked recessive inheritance. Three patients had recurrent disease caused by the bacille Calmette–Guérin vaccine, and the fourth had recurrent tuberculosis. The infections showed tropism for the peripheral lymph nodes. Results: Known autosomal and X-linked genetic aetiologies of MSMD were excluded through genetic and immunological investigations. Genetic linkage analysis of the X-chromosome identified two candidate regions, on Xp11.4–Xp21.2 and Xq25–Xq26.3, with a maximum LOD score of 2. Conclusion: A new X-linked recessive form of MSMD is reported, paving the way for the identification of a new MSMD-causing gene.