Variable expression of WASP in B cell lines of Wiskott-Aldrich syndrome patients.
The Wiskott-Aldrich syndrome (WAS) arises from defects of the X-chromosome gene WASP. Severe platelet defects, thrombocytopenia with small platelets, are a hallmark of the disease, but clinical immunodeficiency based in lymphocyte dysfunction varies from negligible to life threatening among WAS patients. To address the connection between WASP mutations and clinical outcomes, we generated and characterized a panel of patient B cell lines. Three cell lines from patients with exon 2 missense mutations and mild immune dysfunction were found to express substantial levels of WASP mRNA and protein. On the other hand, 8 of 10 cell lines from patients with moderate or severe immune dysfunction lack detectable WASP protein. The findings suggest that the clinical variability of the WAS can partially be explained by the level of WASP protein in the patient's cells.
Remold-O'Donnell
E
E
Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Remold@cbr.med.harvard.edu
Cooley
J
J
Shcherbina
A
A
Hagemann
T L
TL
Kwan
S P
SP
Kenney
D M
DM
Rosen
F S
FS
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014923:Wiskott-Aldrich Syndrome / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein
D011506:Proteins; D012333:RNA, Messenger; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein