Journal ArticleDOI
Mutations in the Mu Heavy-Chain Gene in Patients with Agammaglobulinemia
Leman Yel,Yoshiyuki Minegishi,Elaine Coustan-Smith,Rebecca H. Buckley,Hubert Trübel,Lauren M. Pachman,Geoffrey R. Kitchingman,Dario Campana,Jurg Rohrer,Mary Ellen Conley +9 more
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TLDR
Defects in the mu heavy-chain gene are a cause of agammaglobulinemia in humans, which implies that an intact membrane-bound mu chain is essential for B-cell development.Abstract:
Background Most patients with congenital hypogammaglobulinemia and absent B cells are males with X-linked agammaglobulinemia, which is caused by mutations in the gene for Bruton's tyrosine kinase (Btk); however, there are females with a similar disorder who do not have mutations in this gene. We studied two families with autosomal recessive defects in B-cell development and patients with presumed X-linked agammaglobulinemia who did not have mutations in Btk. Methods A series of candidate genes that encode proteins involved in B-cell signal-transduction pathways were analyzed by linkage studies and mutation screening. Results Four different mutations were identified in the mu heavy-chain gene on chromosome 14. In one family, there was a homozygous 75-to-100-kb deletion that included D-region genes, J-region genes, and the mu constant-region gene. In a second family, there was a homozygous base-pair substitution in the alternative splice site of the mu heavy-chain gene. This mutation would inhibit productio...read more
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Iconographies supplémentaires de l'article : Practice parameter for the diagnosis and management of primary immunodeficiency
Francisco A. Bonilla,David A. Khan,Zuhair K. Ballas,Javier Chinen,Michael M. Frank,Joyce T. Hsu,Michael D. Keller,Lisa Kobrynski,Hirsh D. Komarow,Bruce Mazer,Robert P. Nelson,Jordan S. Orange,John M. Routes,William T. Shearer,Ricardo U. Sorensen,James W. Verbsky,David I. Bernstein,Joann Blessing-Moore,David Lang,Richard A. Nicklas,John Oppenheimer,Jay M Portnoy,Christopher Randolph,Diane E. Schuller,Sheldon L. Spector,S. Tilles,Dana V. Wallace,D.A. Khan +27 more
TL;DR: This document incorporated the efforts of many participants, and no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters.
Journal ArticleDOI
An antibody-deficiency syndrome due to mutations in the CD19 gene
Menno C. van Zelm,Ismail Reisli,Mirjam van der Burg,Diana Castaño,Carel J. M. van Noesel,Maarten J. D. van Tol,Cristina Woellner,Bodo Grimbacher,Pablo J. Patiño,Jacques J.M. van Dongen,José Luis Franco +10 more
TL;DR: In this paper, the CD19 protein forms a complex with CD21, CD81, and CD225 in the membrane of mature B cells, which signals the B cell to decrease its threshold for activation by the antigen.
Journal ArticleDOI
Practice parameter for the diagnosis and management of primary immunodeficiency.
Francisco A. Bonilla,I. Leonard Bernstein,David A. Khan,Zuhair K. Ballas,Javier Chinen,Michael M. Frank,Lisa Kobrynski,Arnold I. Levinson,Bruce Mazer,Robert P. Nelson,Jordan S. Orange,John M. Routes,William T. Shearer,William T. Shearer,Ricardo U. Sorensen +14 more
TL;DR: The present work presents a meta-analysis of the immune checkpoints in the immune system that highlights the importance of knowing these checkpoints before and during the course of treatment with chemotherapy.
Journal ArticleDOI
B-cell biology and development
TL;DR: The combination of susceptible genetic backgrounds with the rescue of self-reactive B cells by T cells allows the generation of autoreactive clones found in patients with many autoimmune diseases and even in those with primary immunodeficiencies.
Journal ArticleDOI
Primary B Cell Immunodeficiencies: Comparisons and Contrasts
Mary Ellen Conley,A. Kerry Dobbs,Dana Farmer,Sebnem Kilic,Kenneth Paris,Sofia Grigoriadou,Elaine Coustan-Smith,Vanessa Howard,Dario Campana +8 more
TL;DR: Identifying the genetic and environmental factors that influence the clinical phenotype may enhance patient care and the understanding of normal B cell development.
References
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Journal ArticleDOI
RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression.
TL;DR: A striking similarity among the rare splice junctions which do not contain AG at the 3' splice site or GT at the 5'splice site indicates the existence of special mechanisms to recognize them, and that these unique signals may be involved in crucial gene-regulation events and in differentiation.
Journal ArticleDOI
A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene
TL;DR: The importance of the membrane form of the μ chain in B-cell development is assessed by generating mice lacking this chain by disrupting one of the membranes exons of the gene encoding the μ-chain constant region by gene targeting in mouse embryonic stem cells.
Journal ArticleDOI
The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases
David Vetrie,Vorechovský I,Paschalis Sideras,Paschalis Sideras,Jill Holland,Angela F. Davies,Frances Flinter,Lennart Hammarström,Christine Kinnon,Roland J. Levinsky,Martin Bobrow +10 more
TL;DR: A novel gene has been isolated which maps to the XLA locus, is expressed in B cells, and shows mutations in families with the disorder, the first evidence that mutations in a src-related gene are involved in human genetic disease.
Journal ArticleDOI
Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia
Satoshi Tsukada,Douglas C. Saffran,David J. Rawlings,Ornella Parolini,Ornella Parolini,R. Cutler Allen,Ivana Klisak,Robert S. Sparkes,Hiromi Kubagawa,Hiromi Kubagawa,Hiromi Kubagawa,T. K. Mohandas,Shirley G. Quan,John W. Belmont,Max D. Cooper,Max D. Cooper,Max D. Cooper,Mary Ellen Conley,Mary Ellen Conley,Owen N. Witte +19 more
TL;DR: A novel cytoplasmic tyrosine kinase, termed BPK (B cell progenitor kinase), which is expressed in all stages of the B lineage and in myeloid cells is described, likely the XLA gene and functions in pathways critical to B cell expansion.
Journal ArticleDOI
Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting.
TL;DR: This work has employed a method based on the Cre-loxP recombination system of bacteriophage P1 to generate a mouse strain in which the JH segments and the intron enhancer in the IgH locus are deleted, and shows that, on the mutant chromosome, switch recombination at the mu gene switch region is strongly suppressed, whereas the switch region of the gamma 1 gene is efficiently rearranged.
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