title: A novel X-linked recessive form of Mendelian susceptibility to mycobaterial disease.
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 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.
  
  
  CONCLUSIONS
  A new X-linked recessive form of MSMD is reported, paving the way for the identification of a new MSMD-causing gene.
authors.affiliation: Laboratoire de Génétique Humaine des Maladies Infectieuses INSERM Unité 550, Faculté Necker, Paris, France.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Orchidée
authors.initials: O
authors.lastname: Filipe-Santos
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Feinberg
authors.forename: Christian
authors.initials: C
authors.lastname: Perronne
authors.forename: Ariane
authors.initials: A
authors.lastname: Chapgier
authors.forename: Ludovic
authors.initials: L
authors.lastname: de Beaucoudrey
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vogt
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lemainque
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000627:therapeutic use; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006099:Granuloma / Q000235:genetics / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008206:Lymphatic Diseases / Q000235:genetics / Q000473:pathology; D008297:Male; D009164:Mycobacterium Infections / Q000235:genetics*; D010375:Pedigree; D012008:Recurrence; D014376:Tuberculosis / Q000235:genetics* / Q000517:prevention & control
chemical_list: D001500:BCG Vaccine