title: Severe infectious diseases of childhood as monogenic inborn errors of immunity.
abstract: This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.
authors.affiliation: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065; Howard Hughes Medical Institute, New York, NY 10065; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U1163, Necker Hospital for Sick Children, 75015 Paris, France; Imagine Institute, Paris Descartes University, 75015 Paris, France; Pediatric Hematology and Immunology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, 75015 Paris, France jean-laurent.casanova@rockefeller.edu.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000293:Adolescent; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology; D002648:Child; D003165:Complement System Proteins / Q000235:genetics; D020803:Encephalitis, Herpes Simplex / Q000235:genetics / Q000276:immunology; D004819:Epidermodysplasia Verruciformis / Q000235:genetics / Q000276:immunology; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology*; D007239:Infections / Q000235:genetics* / Q000276:immunology*; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology; D008288:Malaria / Q000235:genetics / Q000276:immunology; D008957:Models, Genetic; D018448:Models, Immunological; D009164:Mycobacterium Infections / Q000235:genetics / Q000276:immunology; D009343:Neisseria / Q000276:immunology / Q000472:pathogenicity; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology; D014005:Tinea / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D007371:Interferon-gamma; D003165:Complement System Proteins
keywords: human genetics; immunology; infectious diseases; pediatrics; primary immunodeficiency