X-linked thrombocytopenia and Wiskott-Aldrich syndrome: similar regional assignment but distinct X-inactivation pattern in carriers.
While inherited X-linked (XL) isolated thrombocytopenia is a mild condition, the Wiskott-Aldrich syndrome (WAS) associates severe thrombocytopenia with an immunodeficiency component and has a poor prognosis. Whether these conditions correspond to separate genetic entities or to different mutations of the same gene(s) remains unresolved. The Wiskott-Aldrich syndrome locus has been assigned to Xp 11.2 by means of RFLP studies. The X-inactivation pattern in female carriers has been found to follow a skewed pattern in the hematopoietic cells, thus allowing carrier detection. We studied a family with four members affected by XL thrombocytopenia and report the results of genetic segregation analysis, together with the X-inactivation pattern of hematopoietic cells from an obligate female carrier. Although the affected locus mapped to the same region as that of WAS, lymphocytes presented a skewed pattern of X-inactivation, whereas polymorphonuclear lymphocytes (PMN) did not. These results provide further evidence that the Wiskott-Aldrich syndrome and XL thrombocytopenia are different expressions of mutations within a single locus and that the severity of the disease corresponds to distinct hematopoietic cell selections in obligate carriers.
De Saint-Basile
G
G
INSERM U 132, Hôpital des Enfants-Malades, Paris, France.
Schlegel
N
N
Caniglia
M
M
Le Deist
F
F
Kaplan
C
C
Lecompte
T
T
Piller
F
F
Fischer
A
A
Griscelli
C
C
D000328:Adult; D002648:Child; D002675:Child, Preschool; D004303:Dosage Compensation, Genetic; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D013921:Thrombocytopenia / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D014960:X Chromosome