Diagnosis of Wiskott-Aldrich Syndrome by Analysis of the X Chromosome Inactivation Patterns in Maternal Leucocyte Populations Using the Hypervariable DXS255 Locus

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 1991 May 1

PMID 1709069

Citations 8

Authors

R W Hendriks

M de Weers

R G Mensink

M E Kraakman

A J Veerman

L A Sandkuyl

R K Schuurman

Affiliations

Soon will be listed here.

Abstract

The Wiskott-Aldrich syndrome (WAS) is characterized by severe recurrent infections, petachiae and chronic eczema. The syndrome involves differentiation disorders in several haematopoietic cell lineages usually manifested as T lymphocyte deficiency, dysgammaglobulinaemia and thrombocytopenia. The defect is inherited in an X-linked recessive mode. A 1-year-old boy presented with otitis, upper respiratory infections, eczema, a persistent granulocytopenia and a dysgammaglobulinaemia. In his family five males in two generations had been shown to have WAS, which entailed a significant risk for the patient to have WAS. As the WAS gene or gene product is not delineated, the symptoms of the patient presented a diagnostic dilemma. If the boy had inherited the disease, his mother should be a WAS carrier. Segregation analysis in the family using the closely linked restriction fragment length polymorphisms (RFLP) DXS7, DXS255 and DXS14 did not exclude her carriership, although the probability was low. As a result of the differentiation arrest, obligate female WAS carriers manifest a unilateral X chromosome inactivation pattern in several haematopoietic cell lineages. Methylation analysis of the X chromosomal DXS255 loci exposed random X chromosome inactivation patterns in the peripheral blood granulocytes, T lymphocytes and B lymphocytes of the patient's mother. These findings excluded her WAS carriership and therefore excluded the diagnosis of WAS in the patient. This was further substantiated in a 1-year follow up with recovery from the haematological and immunological symptoms. These results demonstrated that X inactivation analysis in maternal leucocytes is decisive in the exclusion of the diagnosis of WAS.

Citing Articles

X chromosome inactivation analysis to distinguish sporadic cases of X-linked agammaglobulinaemia from common variable immunodeficiency.

Tsuge I, Matsuoka H, Abe T, Kamachi Y, Torii S Eur J Pediatr. 1993; 152(11):900-4.

PMID: 8276019 DOI: 10.1007/BF01957526.

Differential methylation at the 5' and the 3' CCGG sites flanking the X chromosomal hypervariable DXS255 locus.

Hendriks R, Kraakman M, Mensink R, Schuurman R Hum Genet. 1991; 88(1):105-11.

PMID: 1959916 DOI: 10.1007/BF00204939.

Genetics of human X-linked immunodeficiency diseases.

Hendriks R, Schuurman R Clin Exp Immunol. 1991; 85(2):182-92.

PMID: 1863997 PMC: 1535742. DOI: 10.1111/j.1365-2249.1991.tb05702.x.

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.

Notarangelo L, Parolini O, Porta F, Locatelli F, Lanfranchi A, Marconi M Hum Genet. 1991; 88(2):237-41.

PMID: 1684569 DOI: 10.1007/BF00206081.

X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.

Gibbons R, Suthers G, Wilkie A, Buckle V, Higgs D Am J Hum Genet. 1992; 51(5):1136-49.

PMID: 1415255 PMC: 1682840.

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