[Molecular genetic diagnosis of Wiskott-Aldrich syndrome].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Orth
U
U
Institut für Humangenetik, Medizinische Universität zu Lübeck.
Rosenkranz
W
W
Schwinger
E
E
Holzgreve
W
W
Gal
A
A
D000328:Adult; D002874:Chromosome Mapping; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008967:Molecular Biology; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012729:Sex Chromosome Aberrations / Q000175:diagnosis / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000175:diagnosis / Q000235:genetics*; D014960:X Chromosome
D005819:Genetic Markers