Hemophilia A: carrier detection and prenatal diagnosis by DNA analysis
M Pecorara, L Casarino, PG Mori, M Morfini, G Mancuso, AM Scrivano, E Boeri, AC Molinari, R De Biasi and N Ciavarella
In this study, we used DNA polymorphisms for carrier detection and prenatal
diagnosis of hemophilia A in a large group of Italian families. The
restriction fragment length polymorphisms (RFLPs) investigated were the
intragenic polymorphic Bc/I site within the factor VIII gene; the
extragenic multiallelic Taq I system at the St14 locus; and the extragenic
Bg/II site at the DX13 locus. The factor VIII probe was informative in 30%,
St14 in 82%, and DX13 in 60% of obligate carriers. The combination of
factor VIII-Bc/I and St14-Taq I showed that 91% of obligate carriers were
heterozygotes for one or both; with all three probes, only 4% of obligate
carriers were noninformative. In families clearly segregating for
hemophilia A, RFLP analysis allowed us to define the carrier status for the
hemophilia A gene in all 27 women tested. RFLP analysis allowed us to
exclude the carrier status in 39 of 45 female relatives of sporadic
patients. The combination of RFLP analysis and biological assay of factor
VIII allowed us to identify a de novo mutation in the maternal grandfather
in 7 of 12 of the families with sporadic cases, for which members of three
generations were available for study. Nine of 10 couples requesting
prenatal diagnosis provided informative RFLP DNA pattern. Carrier status
was excluded in two women, two fetuses were shown to be female, and
prenatal diagnosis was carried out in five pregnancies by DNA analysis.
Prenatal testing was successful in three instances and failed in two
because a sufficient amount of chorionic villous DNA was not obtained for
the analysis.
Volume 70,
Issue 2,
pp. 531-535,
08/01/1987
Copyright © 1987 by The American Society of Hematology
