title: From idiopathic infectious diseases to novel primary immunodeficiencies.
abstract: Primary immunodeficiencies are typically seen as rare monogenic conditions associated with detectable immunologic abnormalities, resulting in a broad susceptibility to multiple and recurrent infections caused by weakly pathogenic and more virulent microorganisms. By opposition to these conventional primary immunodeficiencies, we describe nonconventional primary immunodeficiencies as Mendelian conditions manifesting in otherwise healthy patients as a narrow susceptibility to infections, recurrent or otherwise, caused by weakly pathogenic or more virulent microbes. Conventional primary immunodeficiencies are suspected on the basis of a rare, striking, clinical phenotype and are defined on the basis of an overt immunologic phenotype, often leading to identification of the disease-causing gene. Nonconventional primary immunodeficiencies are defined on the basis of a more common and less marked clinical phenotype, which remains isolated until molecular cloning of the causal gene reveals a hitherto undetected immunologic phenotype. Similar concepts can be applied to primary immunodeficiencies presenting other clinical features, such as allergy and autoimmunity. Nonconventional primary immunodeficiencies thus expand the clinical boundaries of this group of inherited disorders considerably, suggesting that Mendelian primary immunodeficiencies are more common in the general population than previously thought and might affect children with a single infectious, allergic, or autoimmune disease.
authors.affiliation: Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-INSERM U550, Faculté de Médecine Necker, Paris, France. casanova@necker.fr
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Janine
authors.initials: J
authors.lastname: Reichenbach
authors.forename: Natasha
authors.initials: N
authors.lastname: Remus
authors.forename: Horst
authors.initials: H
authors.lastname: von Bernuth
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
mesh_terms: D000361:Agammaglobulinemia / Q000145:classification / Q000235:genetics; D004198:Disease Susceptibility; D030342:Genetic Diseases, Inborn / Q000145:classification / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000145:classification* / Q000150:complications / Q000235:genetics; D007239:Infections / Q000209:etiology*