Vav1 haploinsufficiency in a common variable immunodeficiency patient with defective T-cell function.
Common variable immunodeficiency (CVID) is a primary immune disorder characterized by impaired antibody production, which is in many instances secondary to defective T cell function (T-CVID). We previously identified a subset of T-CVID patients characterized by defective expression of Vav1, a guanine nucleotide exchanger which couples the T-cell antigen receptor to reorganization of the actin cytoskeleton. Here we have addressed the possibility that an intrinsic defect in the Vav1 gene might underlie the reduction in Vav protein observed in T cells from these patients. We report the identification in one T-CVID patient of a heterozygous deletion in Vav1. The gene deletion, spanning exons 2-27, accounts for the reduction in Vav1 mRNA and protein in T cells from this patient. The disease-related pedigree of this patient suggests a de novo origin of the Vav1 deletion. The findings highlights Vav1 as an autosomal dominant disease gene associated with CVID with defective T-cell function.
Department of Evolutionary Biology, University of Siena, Italy.
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Capitani
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Ariani
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Amedei
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Pezzicoli
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Matucci
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Vultaggio
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Troilo
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Renieri
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Baldari
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D' Elios
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology; D015536:Down-Regulation; D005091:Exons; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D057895:Haploinsufficiency; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D051567:Proto-Oncogene Proteins c-vav; D012333:RNA, Messenger; C496618:VAV1 protein, human