Molecular diagnosis of Wiskott-Aldrich syndrome in Taiwan

Yin-Hsiu Chien^1,2, Wuh-Liang Hwu^1,2, Tadashi Ariga³, Kuei-Wen Chang⁴, Yao-Hsu Yang¹, Kai-Hsin Lin¹, Bor-Luen Chiang¹
Departments of ¹Pediatrics and ²Medical Genetics, National Taiwan University Hospital and National Taiwan University, Taipei; ³Department of Human Gene Therapy, Hokkaido University Graduate School of Medicine, Japan; ⁴Department of Pediatrics, Chang Gung Childrens Hospital, Taoyuan, Taiwan, ROC

Received: September 28, 2003 Revised: December 12, 2003 Accepted: February 25, 2004

Corresponding author: Dr. Bor-Luen Chiang, Department of Pediatrics, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan 100, ROC. E-mail:

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.

Key words: Chinese, mutation, prenatal diagnosis, Taiwan, Wiskott-Aldrich syndrome, X-inactivation

J Microbiol Immunol Infect 2004;37:276-281.