Analysis of genetic defects in patients with the common variable immunodeficiency phenotype in a single Taiwanese tertiary care hospital.
BACKGROUND
Seven known genetic defects, including Bruton tyrosine kinase (Btk), CD4OL, and signaling lymphocyte activation molecule-associated protein (SAP) (all X-linked) and inducible costimulator molecule (ICOS), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B-cell-activating factor of the tumor necrosis family receptor (BAFFR), and CD19 (all autosomal recessive), were found in patients with the phenotype of common variable immunodeficiency (CVID).


OBJECTIVE
To investigate these 7 candidate protein expressions and candidate gene sequences for comprehensive analysis of known genetic defects in patients with CVID.


METHODS
These 7 candidate protein expressions were evaluated by flow cytometry or Western blot, and candidate genes were evaluated by direct sequencing.


RESULTS
Of 9 CVID patients from a single Taiwanese tertiary care hospital, we identified 2 cousins with decreased Btk expression who had a mutated (Asp521Val) kinase domain of Btk (1694A>T in exon 15) and 1 patient with decreased CD40L expression who had a mutated (Thr254Met) extracellular domain of CD40L (782T>C in exon 5).


CONCLUSIONS
This comprehensive approach revealed that, in Taiwan, in some patients mild forms of X-linked agammaglobulinemia and hyper-IgM syndrome caused the CVID phenotype. No mutations of SAP, ICOS, TACI, BAFFR, and CD19 were identified in this study, although selection bias among the small study population and genetic variation may exist.
Lee
Wen-I
WI
Department of Pediatric Allergy, Immunology and Rheumatology, Chang Gung University College of Medicine, Chang Gung Children's Hospital, Taoyuan, Taiwan. leeweni@adm.cgmh.org.tw
Huang
Jing-Long
JL
Kuo
Ming-Ling
ML
Lin
Syh-Jae
SJ
Chen
Li-Chen
LC
Chen
Mai-Tzu
MT
Jaing
Tang-Her
TH
D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D018941:Antigens, CD19 / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D053265:B-Cell Activation Factor Receptor / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D023201:CD40 Ligand / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000235:genetics; D060889:Inducible T-Cell Co-Stimulator Protein; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013624:Taiwan; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics
D018941:Antigens, CD19; D000945:Antigens, Differentiation, T-Lymphocyte; D053265:B-Cell Activation Factor Receptor; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D023201:CD40 Ligand; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human