XXXX : carrier detection and prenatal diagnosis by DNA analysis.

@entity1 @entity57319 @entity447
In this study, we used DNA polymorphisms for carrier detection and prenatal diagnosis of @entity447 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 @entity57319 locus; and the extragenic Bg/II site at the DX13 locus. The factor VIII probe was informative in 30%, @entity57319 in 82%, and DX13 in 60% of obligate carriers. The combination of factor VIII-Bc/I and @entity57319 -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 @entity447 , RFLP analysis allowed us to define the carrier status for the @entity447 gene in all 27 @entity1 tested. RFLP analysis allowed us to exclude the carrier status in 39 of 45 female relatives of sporadic @entity1 . 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 @entity1 , 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.
