A PCR-based non-radioactive X-chromosome inactivation assay for genetic counseling in X-linked primary immunodeficiencies.
The Wiskott-Aldrich syndrome (WAS), X-linked severe combined immunodeficiency (SCIDX1), and X-linked agammaglobulinemia (XLA) are severe congenital immunodeficiencies with X-linked inheritance. Although rare, they are all associated with severe infections from early in life, and high morbidity and mortality. Female carriers of these diseases can be identified by a non-random pattern of X-chromosomal inactivation in cell lineages targeted by each gene defect. For patients with WAS, SCIDX1 or XLA, the demonstration of non random X-Chromosome inactivation in their mothers can be used to confirm clinical diagnosis. Furthermore, analysis of X-Chromosome inactivation in at risk females allows preconceptional carrier detection, thus representing an important aid in genetic counseling. For each disease we established a PCR-based, non radioactive assay at the human androgen receptor (HUMARA) locus, that allows analysis of X-Chromosome inactivation in the affected cell types and in tissue specific controls to exclude the issue of skewed X-chromosomal inactivation. In our study, 50 females with a known family history of XLA [19], WAS [18], and SCIDX1 [13],were examined. A carrier status was established in 19 females (7 XLA, 6 WAS, 6 SCIDX1) and excluded in 29 ( 11 XLA, 11 WAS, 7 SCIDX1). Only in 2 cases (4%) the assay was not informative.
Wengler
G S
GS
Department of Pediatrics, University of Brescia, Italy. wengler@master.cci.unibs.it
Parolini
O
O
Fiorini
M
M
Mella
P
P
Smith
H
H
Ugazio
A G
AG
Notarangelo
L D
LD
D019070:Cell Lineage; D002469:Cell Separation; D004303:Dosage Compensation, Genetic; D005260:Female; D005434:Flow Cytometry; D005817:Genetic Counseling; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods*; D011944:Receptors, Androgen / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics*
D011944:Receptors, Androgen