[Improvement of gene analysis method in hemophilia A and its application of prenatal diagnosis].
OBJECTIVE
To establish a simple and rapid system for carrier detection and prenatal diagnosis in hemophilia A (CHA) family.


METHODS
Long distance-polymerase chain reaction (LD-PCR) was selected for detection factor VIII intron 22 inversion. Polymorphism of factor VIII intragenic restriction fragment length polymorphism (RFLP) of Xba I and Hin d III, short tandem repeat (STR) within intron 13 and 22, as well as extragenic DXS52 (ST 14) variable number of tandem repeat (VNTR) were assayed by PCR and linkage analysis.


RESULTS
Seventy-one females were diagnosed as carriers within 52 HA families. Twenty-one families were diagnosed to be factor VIII intron 22 inversion and 28 families were diagnosed by linkage analysis, whereas 3 families could not been diagnosed. Seventeen of 18 fetuses at risk were male. Ten of 17 male fetuses were shown to be affected and were subsequently aborted. Seven male fetuses were diagnosed to be not affected. One female fetus was identified to be HA carrier. One-year follow-up study demonstrated that these babies were normal and living well.


CONCLUSIONS
LD-PCR combined with multiple locus linkage analysis enables the direct and indirect detection of HA for carrier testing and prenatal diagnosis.
Liang
Yan
Y
Basic Medical Research Center, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020 P. R. China.
Zhao
Yun
Y
Wang
Zhan-yong
ZY
Yan
Mei
M
Xiao
Bai
B
Liu
Jing-zhong
JZ
D005169:Factor VIII / Q000235:genetics; D005192:Family Health; D005260:Female; D006467:Hemophilia A / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
D005169:Factor VIII