title: Molecular diagnosis of Wiskott-Aldrich syndrome in Taiwan.
abstract: The spectrum of Wiskott-Aldrich syndrome (WAS) mutation in Han Chinese residing in Taiwan has not been previously reported. We describe a multidisciplinary approach to the molecular diagnosis of WAS which could be applied to clinical diagnosis, carrier prediction, and prenatal diagnosis. A total of 6 male patients, from 6 independent families, were referred for the molecular diagnosis of WAS. The respective methylation status of the 6 X chromosomes in peripheral blood leukocytes from obligatory female carriers was analyzed initially, followed by analysis of the level of expression of WAS protein (WASP) in peripheral leukocytes from patients, using a Western blotting technique. The analysis of the specific WAS gene mutation was done by direct sequencing. Mutations were identified in the WAS gene of all patients. Mutations identified included p.R13X, p.R41X, p.S82P, IVS1-1 G --> C, p.L342TFsX493, and a large deletion. Four patients had no WASP expression in peripheral leukocytes obtained before bone marrow transplantation. Several female carriers in the families of the 6 patients with such mutations were confirmed. One prenatal diagnosis was made in a fetus and he did not inherit the mutation. The importance of mutations in the first 2 exons of the WAS gene was demonstrated in this study, which represented 5 of the 6 mutations identified in 6 patients. The use of a multidisciplinary approach including DNA and protein analysis is required for molecular diagnosis and genetic counseling of WAS.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.forename: Kuei-Wen
authors.initials: KW
authors.lastname: Chang
authors.forename: Yao-Hsu
authors.initials: YH
authors.lastname: Yang
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Lin
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011506:Proteins / Q000235:genetics*; D013624:Taiwan; D014923:Wiskott-Aldrich Syndrome / Q000175:diagnosis* / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D018076:DNA, Complementary; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein