[Molecular genetic diagnosis of Wiskott-Aldrich syndrome]

Wiskott-Aldrich syndrome is a severe X-linked recessive disorder of the hematopoietic system. The gene locus for Wiskott-Aldrich syndrome was mapped on the proximal short arm of the X chromosome by demonstrating close linkage to the loci DXS255 and TIMP. Carriers for Wiskott-Aldrich syndrome are asymptomatic and, hence, can not be identified clinically.

For a better estimate of the carrier risk of female family members, an extended molecular genetic analysis has been carried out on two kindreds with Wiskott-Aldrich syndrome: We followed the allele segregation at the two marker loci mentioned above known to be closely linked to the disease locus (indirect genotype diagnostics); in addition, we determined the pattern of X-inactivation by analyzing the methylation status of the two X chromosomes.

We show that carriers for Wiskott-Aldrich syndrome can reliably be identified by the combination of segregation and X chromosome inactivation studies. Helpful information can be obtained by such studies in sporadic cases, too, or in families, in which--due to the early death--no surviving affected males are available for an DNA study.

Indirect genotype analysis combined with the study of X-inactivation pattern is a valuable diagnostic tool for genetic counselling of families with Wiskott-Aldrich syndrome.