Analysis of X-chromosome inactivation and presumptive expression of the Wiskott-Aldrich syndrome (WAS) gene in hematopoietic cell lineages of a thrombocytopenic carrier female of WAS.
We report on a thrombocytopenic female belonging to a pedigree with the Wiskott-Aldrich syndrome (WAS). Restriction fragment length polymorphism (RFLP) analysis with probe M27 beta, closely linked to the WAS gene, demonstrated that she is a carrier of WAS. Both small-sized and normal-sized platelets were present, suggesting that, unlike the vast majority of WAS carriers, she does not manifest nonrandom X-chromosome inactivation in the thrombopoietic cell lineage. Study of X-chromosome inactivation by means of RFLP and methylation analysis demonstrated that the pattern of X-chromosome inactivation was nonrandom in T lymphocytes, but random in granulocytes. While this is the first complete report on the occurrence of thrombocytopenia in a carrier female of WAS as the result of atypical lyonization, it also suggests that expression of the WAS gene occurs at (or extends up to) a later stage than the multipotent stem cell along the hematopoietic differentiation pathway.
Notarangelo
L D
LD
Department of Pediatrics, University of Brescia, Italy.
Parolini
O
O
Porta
F
F
Locatelli
F
F
Lanfranchi
A
A
Marconi
M
M
Nespoli
L
L
Albertini
A
A
Craig
I W
IW
Ugazio
A G
AG
D004303:Dosage Compensation, Genetic; D015870:Gene Expression / Q000235:genetics; D006098:Granulocytes; D006412:Hematopoietic Stem Cells; D006579:Heterozygote; D006801:Humans; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D013601:T-Lymphocytes; D013921:Thrombocytopenia / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D014960:X Chromosome