title: X-linked thrombocytopenia and Wiskott-Aldrich syndrome: similar regional assignment but distinct X-inactivation pattern in carriers.
abstract: 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.
authors.affiliation: INSERM U 132, Hôpital des Enfants-Malades, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: De Saint-Basile
authors.forename: N
authors.initials: N
authors.lastname: Schlegel
authors.forename: M
authors.initials: M
authors.lastname: Caniglia
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: C
authors.initials: C
authors.lastname: Kaplan
authors.forename: T
authors.initials: T
authors.lastname: Lecompte
authors.forename: F
authors.initials: F
authors.lastname: Piller
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: C
authors.initials: C
authors.lastname: Griscelli
mesh_terms: 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