A PCR-based non-radioactive X-chromosome inactivation assay for genetic counseling in X-linked primary immunodeficiencies

Georg S. Wengler, Ornella Parolini, Maurilia Fiorini, Patrizia Mella, Hedy Smith, Alberto G. Ugazio, Luigi D. Notarangelo

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1405-1411
Number of pages7
JournalLife Sciences
Volume61
Issue number14
DOIs
Publication statusPublished - Nov 29 1997

Fingerprint

X-Linked Combined Immunodeficiency Diseases
X Chromosome Inactivation
Wiskott-Aldrich Syndrome
Genetic Counseling
Chromosomes
Assays
Polymerase Chain Reaction
Demonstrations
Genes
Tissue
X-Linked Genes
Defects
Cell Lineage
Mothers
Bruton type agammaglobulinemia
Morbidity
Mortality
Infection

Keywords

  • HUMARA-PCR
  • Non-radioactive X-chromosome inactivation assay
  • Primary immunodeficiency
  • X-chromosome inactivation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Wengler, G. S., Parolini, O., Fiorini, M., Mella, P., Smith, H., Ugazio, A. G., & Notarangelo, L. D. (1997). A PCR-based non-radioactive X-chromosome inactivation assay for genetic counseling in X-linked primary immunodeficiencies. Life Sciences, 61(14), 1405-1411. https://doi.org/10.1016/S0024-3205(97)00686-3

A PCR-based non-radioactive X-chromosome inactivation assay for genetic counseling in X-linked primary immunodeficiencies. / Wengler, Georg S.; Parolini, Ornella; Fiorini, Maurilia; Mella, Patrizia; Smith, Hedy; Ugazio, Alberto G.; Notarangelo, Luigi D.

In: Life Sciences, Vol. 61, No. 14, 29.11.1997, p. 1405-1411.

Research output: Contribution to journalArticle

Wengler, GS, Parolini, O, Fiorini, M, Mella, P, Smith, H, Ugazio, AG & Notarangelo, LD 1997, 'A PCR-based non-radioactive X-chromosome inactivation assay for genetic counseling in X-linked primary immunodeficiencies', Life Sciences, vol. 61, no. 14, pp. 1405-1411. https://doi.org/10.1016/S0024-3205(97)00686-3
Wengler, Georg S. ; Parolini, Ornella ; Fiorini, Maurilia ; Mella, Patrizia ; Smith, Hedy ; Ugazio, Alberto G. ; Notarangelo, Luigi D. / A PCR-based non-radioactive X-chromosome inactivation assay for genetic counseling in X-linked primary immunodeficiencies. In: Life Sciences. 1997 ; Vol. 61, No. 14. pp. 1405-1411.
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