title: Discovery of single-gene inborn errors of immunity by next generation sequencing.
abstract: Many patients with clinical and laboratory evidence of primary immunodeficiency do not have a gene specific diagnosis. The use of next generation sequencing, particularly whole exome sequencing, has given us an extraordinarily powerful tool to identify the disease-causing genes in some of these patients. At least 34 new gene defects have been identified in the last 4 years. These findings document the striking heterogeneity of the phenotype in patients with mutations in the same gene. In some cases this can be attributed to loss-of-function mutations in some patients, but gain-of-function mutations in others. In addition, the surprisingly high frequency of autosomal dominant immunodeficiencies with variable penetrance, and de novo mutations in disorders with a severe phenotype has been unmasked.
authors.affiliation: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Electronic address: mconley@rockefeller.edu.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Conley
authors.affiliation: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris Descartes University and INSERM, Imagine Institute, Necker Hospital for Sick Children, Paris, France; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005091:Exons; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000276:immunology; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010641:Phenotype