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Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency
Author(s) -
Notarangelo Luigi D.,
Mella Patrizia,
Jones Alison,
de Saint Basile Genevieve,
Savoldi Gianfranco,
Cranston Treena,
Vihinen Mauno,
Schumacher Richard Fabian
Publication year - 2001
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1188
Subject(s) - biology , severe combined immunodeficiency , common gamma chain , primary immunodeficiency , immune system , janus kinase 3 , gene , mutation , hematopoietic stem cell transplantation , genetics , immunodeficiency , stem cell , immunology , t cell , antigen presenting cell , interleukin 10
During the last 10 years, an increasing number of genes have been identified whose abnormalities account for primary immunodeficiencies, with defects in development and/or function of the immune system. Among them is the JAK3 ‐gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which share the common gamma chain. Defects of this gene cause an autosomal recessive form of severe combined immunodeficiency with almost absent T‐cells and functionally defective B‐cells (T – B + SCID). Herewith, we present molecular information on the first 27 unique mutations identified in the JAK3 gene, including clinical data on all of the 23 affected patients reported so far. A variety of mutations scattered throughout all seven functional domains of the protein, and with different functional effects, have been identified. Availability of a molecular screening test, based on amplification of genomic DNA, facilitates the diagnostic approach, and has permitted recognition that JAK3 deficiency may also be associated with atypical clinical and immunological features. Development of a structural model of the JAK3 kinase domain has allowed characterization of the functional effects of the various mutations. Most importantly, molecular analysis at the JAK3 locus results in improved genetic counseling, allows early prenatal diagnosis, and prompts appropriate treatment (currently based on hematopoietic stem cell transplantation) in affected families. Hum Mutat 18:255–263, 2001. © 2001 Wiley‐Liss, Inc.