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 gamma-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.
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 gamma-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.
Authors: R Döffinger; A Smahi; C Bessia; F Geissmann; J Feinberg; A Durandy; C Bodemer; S Kenwrick; S Dupuis-Girod; S Blanche; P Wood; S H Rabia; D J Headon; P A Overbeek; F Le Deist; S M Holland; K Belani; D S Kumararatne; A Fischer; R Shapiro; M E Conley; E Reimund; H Kalhoff; M Abinun; A Munnich; A Israël; G Courtois; J L Casanova Journal: Nat Genet Date: 2001-03 Impact factor: 38.330
Authors: Sergio D Rosenzweig; Susan E Dorman; Gulbu Uzel; Stephen Shaw; Amy Scurlock; Margaret R Brown; Rebecca H Buckley; Steven M Holland Journal: J Immunol Date: 2004-09-15 Impact factor: 5.422
Authors: Claire Fieschi; Stéphanie Dupuis; Emilie Catherinot; Jacqueline Feinberg; Jacinta Bustamante; Adrien Breiman; Frédéric Altare; Richard Baretto; Françoise Le Deist; Samer Kayal; Hartmut Koch; Darko Richter; Martin Brezina; Guzide Aksu; Phil Wood; Suliman Al-Jumaah; Miquel Raspall; Alberto José Da Silva Duarte; David Tuerlinckx; Jean-Louis Virelizier; Alain Fischer; Andrea Enright; Jutta Bernhöft; Aileen M Cleary; Christiane Vermylen; Carlos Rodriguez-Gallego; Graham Davies; Renate Blütters-Sawatzki; Claire-Anne Siegrist; Mohammad S Ehlayel; Vas Novelli; Walther H Haas; Jacob Levy; Joachim Freihorst; Sami Al-Hajjar; David Nadal; Dewton De Moraes Vasconcelos; Olle Jeppsson; Necil Kutukculer; Klara Frecerova; Isabel Caragol; David Lammas; Dinakantha S Kumararatne; Laurent Abel; Jean-Laurent Casanova Journal: J Exp Med Date: 2003-02-17 Impact factor: 14.307