Clinical aspects and genetic analysis of Taiwanese patients with Wiskott-Aldrich syndrome protein mutation: The first identification of X-linked thrombocytopenia in the Chinese with novel mutations
Journal
Journal of Clinical Immunology
Journal Volume
30
Journal Issue
4
Pages
593-601
Date Issued
2010
Author(s)
Abstract
Background: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, and recurrent infections. However, the more than 500 patient mutations described are mainly based on Caucasian and Japanese populations. This study investigated Taiwanese patients with WASP mutations since 1985 as part of a long-term comprehensive study in primary immunodeficiency diseases (PIDs) covering 23 million inhabitants. Methods: Clinical manifestations, immunologic functions, and WASP gene sequencing and expressions were analyzed in WAS patients. And, those patients with idiopathic thrombocytopenic purpura and "small" thrombocytopenia were enrolled. Results: Of 16 patients studied in 1993-2009, 12 presented as classic WAS phenotype and four had X-linked thrombocytopenia (XLT). Almost all correlated to the WASP expression level and severity of infections. Causes of mortality in the 12 classic WAS patients were mass bleeding, Staphylococcus aureus sepsis, and cytomegalovirus (CMV) pneumonitis in three non-transplant cases, and EBV-associated lymphoproliferative disorder and CMV pneumonitis in two non-engrafted transplant patients. Splicing mutations of Int 8 (+5) G>A in cousins and insertion of 1023 C in unrelated families presented as both XLT and classic WAS phenotype in the same mutations. Four XLT patients, including two novel mutations of 1023 Ins C (in 2) and "double" missense mutations of 1378 C>T and 1421 T>C had relatively higher CD4+ memory cells and/or activated lymphocytes (CD3+CD69+) compared with those of classic WAS patients. Conclusions: The lower ratio of XLT to classic WAS patients underestimates the burden of Taiwanese patients with WASP mutations, especially the XLT phenotype. A clustering pattern on exon 1 and five unique mutations (deletion of 45-48 ACCA, IVS 1 (-1) G>C, large deletion of promoter and exon 1 and 2, insertion 1023 C, and 1378 C>T and 1421 T>C) explain the genetic variations in different ethnic groups, despite the possibility of selection and ascertainment bias. ? Springer Science+Business Media, LLC 2010.
Subjects
Chinese; Genetic analysis; Primary immunodeficiency diseases (PIDs); Taiwan; Wiskott-Aldrich syndrome (WAS); X-linked thrombocytopenia (XLT)
SDGs
Other Subjects
CD16 antigen; CD19 antigen; CD3 antigen; CD69 antigen; cyclosporin A; famciclovir; ganciclovir; gene product; immunoglobulin; immunoglobulin A; immunoglobulin E; immunoglobulin G; immunoglobulin M; methotrexate; methylprednisolone; protein WAS; unclassified drug; Wiskott Aldrich syndrome protein; adolescent; adult; article; autoimmune hemolytic anemia; bleeding; bronchiectasis; CD4 lymphocyte count; CD4+ T lymphocyte; CD8+ T lymphocyte; child; Chinese; clinical article; clinical feature; cord blood stem cell transplantation; cytomegalovirus infection; disease severity; Epstein Barr virus infection; ethnicity; exon; exon skipping; family history; female; frameshift mutation; gene expression; gene insertion; gene mutation; gene sequence; genetic analysis; genetic variability; glomerulonephritis; graft versus host reaction; hematopoietic stem cell transplantation; heterozygote; human; idiopathic thrombocytopenic purpura; immunoglobulin blood level; infection; intron; longitudinal study; lymphocyte activation; lymphocyte proliferation; lymphoproliferative disease; male; memory cell; memory T lymphocyte; missense mutation; mortality; natural killer cell mediated cytotoxicity; nonsense mutation; nucleic acid base substitution; phenotype; pregnancy; priority journal; prognosis; promoter region; protein expression; relative; splenectomy; splicing mutation; staphylococcal bacteremia; thrombocyte transfusion; thrombocytopenia; virus pneumonia; Wiskott Aldrich syndrome; X linked thrombocytopenia; Asian continental ancestry group; cause of death; ethnology; family; genetics; mutation; nucleotide sequence; Taiwan; thrombocytopenia; Wiskott Aldrich syndrome; X chromosome linked disorder; Asian Continental Ancestry Group; Cause of Death; DNA Mutational Analysis; Family; Genetic Diseases, X-Linked; Humans; Mutation; Taiwan; Thrombocytopenia; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein; Asian Continental Ancestry Group; Cause of Death; DNA Mutational Analysis; Family; Genetic Diseases, X-Linked; Humans; Mutation; Taiwan; Thrombocytopenia; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
Type
journal article