TY - JOUR
T1 - Wiskott-Aldrich syndrome in a female with skewed X-chromosome inactivation
AU - Andreu, Nuria
AU - Pujol-Moix, Núria
AU - Martinez-Lostao, Luis
AU - Oset, Marta
AU - Muñiz-Diaz, Eduardo
AU - Estivill, Xavier
AU - Volpini, Victor
AU - Fillat, Cristina
PY - 2003/1/1
Y1 - 2003/1/1
N2 - 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. © 2003 Elsevier Inc. All rights reserved.
AB - 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. © 2003 Elsevier Inc. All rights reserved.
KW - Carrier
KW - Platelets
KW - Skewed X-chromosome inactivation
KW - Thrombocytopenia
KW - Wiskott-Aldrich syndrome
U2 - 10.1016/S1079-9796(03)00168-2
DO - 10.1016/S1079-9796(03)00168-2
M3 - Article
VL - 31
SP - 332
EP - 337
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
SN - 1079-9796
IS - 3
ER -