title: Wiskott-Aldrich syndrome in a female with skewed X-chromosome inactivation.
abstract: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by immunodeficiency, eczema, and thrombocytopenia with small platelets. The phenotype of affected males is usually severe, although female carriers of the disorder have no clinical signs of the genetic defect. This is explained by the preferential selection of the normal, nonmutated X-chromosome, as the active allele in hematopoietic cells. In the present article we describe a female case of WAS, with a G-to-A transition in the WASP gene at nucleotide 291. She displays mild thrombocytopenia, with both normal and small-sized platelets. A methylation analysis of the HUMARA gene showed a nonrandom X-chromosome inactivation pattern in which the X-chromosome carrying the normal WASP gene was preferentially inactivated, leaving the mutant gene active. Thus, our results suggest that skewed X-inactivation, favoring the WASP-mutated allele, is the mechanism underlying the WAS phenotype of this girl. Moreover the results alert us to the fact that particular females, with a family history of WAS, may develop certain signs of the disease.
authors.affiliation: Programa Gens i malaltia, Centre de Regulació Genòmica, Passeig Marítim 37-49, Barcelona 08003, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Andreu
authors.forename: Núria
authors.initials: N
authors.lastname: Pujol-Moix
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Lostao
authors.forename: Marta
authors.initials: M
authors.lastname: Oset
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñiz-Diaz
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Victor
authors.initials: V
authors.lastname: Volpini
authors.forename: Cristina
authors.initials: C
authors.lastname: Fillat
mesh_terms: D000293:Adolescent; D001792:Blood Platelets / Q000648:ultrastructure; D041321:Chromosomes, Human, X / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D013921:Thrombocytopenia / Q000235:genetics; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein