Carrier detection and prenatal diagnosis of X-linked agammaglobulinemia.
We investigated the pregnant mother of a boy with X-linked agammaglobulinemia (XLA) but with no family history of immune disease. The X-inactivation pattern was found, using a methylation-sensitive probe, to be skewed in the maternal B cells but random in the polymorphonuclear cells, indicating carrier status and a 50% risk of inheritance for her male fetus. Using probes assigned to regions on either side of the XLA locus and defining RFL polymorphism, we excluded for the first time a diagnosis of XLA on a chorionic villus sample, with a risk of error less than 0.003. Immunological studies performed at the 19th week of gestation and 3 days after birth confirmed normality. Carrier detection based on the X-chromosome inactivation pattern, together with prenatal studies using probes close to the disease locus, thus permits prenatal diagnosis in families with isolated cases of XLA.
Journet
O
O
INSERM U 132, Hôpital des Enfants-Malades, Paris, France.
Durandy
A
A
Doussau
M
M
Le Deist
F
F
Couvreur
J
J
Griscelli
C
C
Fischer
A
A
de Saint-Basile
G
G
D000361:Agammaglobulinemia / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D002648:Child; D004303:Dosage Compensation, Genetic; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D014960:X Chromosome