Mutational analysis of the WASP gene in 2 Korean families with Wiskott-Aldrich syndrome.
Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by thrombocytopenia with undersized platelets, eczema, and immune deficiency, is caused by mutations in the WASP gene. In this study, we investigated WASP gene mutations and WASP protein expression in 2 unrelated Korean WAS patients. Flow cytometry was used to evaluate WASP expression in lymphocytes. Two previously reported nonsense mutations (Arg211stop and Arg13stop) were identified in this study, a finding that suggested these codons are mutational hotspots. Both mothers showed normal WASP expression in flow cytometric analysis, even though they had heterozygotic patterning, which is indicative of carrier status. Furthermore, an X-chromosome inactivation assay revealed that these carrier mothers had skewed X inactivation. To our knowledge, this is the first report on molecular diagnosis of WAS in Korea. In addition, we detected normal WASP expression in lymphocytes from carrier mothers, a finding consistent with the data on skewed X inactivation.
Jo
Eun-Kyeong
EK
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea.
Futatani
Takeshi
T
Kanegane
Hirokazu
H
Kubota
Takeo
T
Lee
Young-Ho
YH
Jung
Jin-A
JA
Song
Chang-Hwa
CH
Park
Jeong-Kyu
JK
Nonoyama
Shigeaki
S
Miyawaki
Toshio
T
D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004303:Dosage Compensation, Genetic; D005192:Family Health; D005434:Flow Cytometry; D006801:Humans; D007723:Korea; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D010375:Pedigree; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein
D018389:Codon, Nonsense; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein