Genetic counseling in two particular hemophilia A families

Objective To perform genetic counseling of hemophilia A families under particular conditions. Methods The Intron 22 inversion detection and DNA sequencing of all coding regions of factor Ⅷ were established to identify the disease responsible mutations directly. The F8C gene related polymorphisms, including VNTR DXS52, Bcll RFLP and STRs within intron 13 and intron 22, were adopted in the linkage analysis in the pedigree. Results The direct nucleotide sequencing revealed a validated missense mutation R2209Q in exon 24 of F8C gene in pedigree 1 which was uninformative by means of intron 22 inversion detection and indirect linkage analysis. The mutation presented in heterozygous state in the patients sister and her delivery of a normal male fetus corroborated the prenatal genetic diagnosis performed in the same way. The proband of pedigree 2 died years ago and neither mutations nor intron 22 inversion was detected in his daughter, who was sure to be the carrier. The linkage analysis among the available pedigree members, however, excluded the possibility of the transduction of the affected allele to the niece of the proband, who asked for genetic counseling. Conclusions It is feasible to establish carrier and prenatal diagnosis in some special pedigrees of hemophilia A with both direct and indirect protocols.