title: Novel mutations in a Japanese patient with CD19 deficiency.
abstract: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent bacterial infections, hypogammaglobulinemia and low to normal numbers of circulating B cells. Mutations in the ICOS, TACI and CD19 genes have recently been identified in <10% of CVID patients. We, herein, describe two novel CD19 gene disruptions in an 8-year-old Japanese boy, who had been clinically diagnosed as having CVID at the age of 5 years. Flow-cytometric analysis demonstrated absence of CD19 and reduced CD21 expression on CD20-postive peripheral blood B cells. Mutation analysis of CD19 revealed a mutation in the splice acceptor site of intron 5 (IVS5-1G>T) of the maternal allele, resulting in skipping of exon 6, and a truncated protein product. The paternal allele was disrupted by a gross deletion encompassing at least the ATP2A1, CD19 and NFATC2IP genes. The patient had a small number of IgD(-) CD27(+) memory B cells, in which somatic mutation were detected. His B cells showed substantial proliferation upon stimulation, but reduced IgG and IgA production in vitro. These findings extend the mutation spectrum of the CD19 deficiency to four, and confirm the homogeneity of the CD19 deficiency as a unique type of CVID.
authors: Department of Pediatrics, Graduate School of Medicine, University of Toyama, Toyama, Japan. kanegane@med.u-toyama.ac.jp
authors: H
authors: H
authors: Kanegane
authors: K
authors: K
authors: Agematsu
authors: T
authors: T
authors: Futatani
authors: M M
authors: MM
authors: Sira
authors: K
authors: K
authors: Suga
authors: T
authors: T
authors: Sekiguchi
authors: M C
authors: MC
authors: van Zelm
authors: T
authors: T
authors: Miyawaki
mesh_terms: D000595:Amino Acid Sequence; D018941:Antigens, CD19 / Q000032:analysis / Q000235:genetics*; D018951:Antigens, CD20 / Q000032:analysis / Q000378:metabolism; D044466:Asian People; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis; D007156:Immunologic Memory / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D050778:NFATC Transcription Factors / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D017464:Receptors, Complement 3d / Q000032:analysis / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D007072:Immunoglobulin D; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D022821:RNA Splice Sites; D017464:Receptors, Complement 3d; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506943:ATP2A1 protein, human