scholarly journals Hemophilia A: carrier detection and prenatal diagnosis by DNA analysis

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 531-535 ◽  
Author(s):  
M Pecorara ◽  
L Casarino ◽  
PG Mori ◽  
M Morfini ◽  
G Mancuso ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Factor Viii ◽  
Dna Analysis ◽  
Hemophilia A ◽  
De Novo ◽  
Rflp Analysis ◽  
Carrier Detection ◽  
Dna Polymorphisms ◽  
De Novo Mutation ◽  
Carrier Status

Abstract 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.

scholarly journals Hemophilia A: carrier detection and prenatal diagnosis by DNA analysis

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 531-535
Author(s):  
M Pecorara ◽  
L Casarino ◽  
PG Mori ◽  
M Morfini ◽  
G Mancuso ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Factor Viii ◽  
Dna Analysis ◽  
Hemophilia A ◽  
De Novo ◽  
Rflp Analysis ◽  
Carrier Detection ◽  
Dna Polymorphisms ◽  
De Novo Mutation ◽  
Carrier Status

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.

De novo mutation in hemophilia A established by DNA haplotype analysis and precluding prenatal diagnosis

1986 ◽  
Vol 74 (3) ◽  
Author(s):  
M. Delpech ◽  
N Deburgrave ◽  
M. Baudis ◽  
P. Maissonneuve ◽  
J.M. Bardin ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Haplotype Analysis ◽  
Hemophilia A ◽  
De Novo ◽  
De Novo Mutation

Case Report: Development of Factor VIII Inhibitor in a Patient with an Uncommon de novo Mutation in the Factor VIII Gene

2019 ◽  
Vol 141 (3) ◽  
pp. 129-134
Author(s):  
Kirk D. Wyatt ◽  
Lea M. Coon ◽  
Dawn N. Rusk ◽  
Vilmarie Rodriguez ◽  
Deepti M. Warad
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
De Novo ◽  
De Novo Mutation ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Factor Viii Gene ◽  
Patient Reported ◽  
Viii Inhibitor ◽  
Mixed Ethnicity

The development of factor VIII inhibitors remains a significant clinical challenge in the management of hemophilia A. We present a patient of mixed ethnicity with severe hemophilia A who was found to have a F8 gene hemizygous c.5815G>T mutation resulting in an Ala1939Ser substitution (Ala1920Ser in legacy nomenclature) and possible splice site change that has been reported in only 1 patient previously. He developed an inhibitor shortly after starting replacement recombinant factor VIII (Advate®; Baxalta, Bannockburn, IL, USA) and was successfully treated with immune tolerance therapy. Our report describes the second patient reported to have severe hemophilia due to this mutation and the only case of a factor VIII inhibitor associated with this mutation.

The contribution of DNA analysis to carrier detection and prenatal diagnosis of hemophilia A and B

1992 ◽  
Vol 64 (1) ◽  
pp. 2-11 ◽  
Author(s):  
A. H. J. T. Bröcker-Vriends ◽  
E. Bakker ◽  
H. H. H. Kanhai ◽  
G. J. B. van Ommen ◽  
P. H. Reitsma ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Dna Analysis ◽  
Hemophilia A ◽  
Carrier Detection

Combined Use of DNA Probes in First-Trimester Prenatal Diagnosis of Hemophilia A

1987 ◽  
Vol 58 (04) ◽  
pp. 988-992 ◽  
Author(s):  
M Sampietro ◽  
G Camerino ◽  
M Romano ◽  
M D Cappellini ◽  
G Fiorelli ◽  
...  
Keyword(s):  
At Risk ◽  
Prenatal Diagnosis ◽  
Factor Viii ◽  
Dna Analysis ◽  
Hemophilia A ◽  
Chorionic Villus ◽  
Great Majority ◽  
First Trimester ◽  
Fetal Plasma ◽  
Combined Use

SummaryFirst-trimester prenatal diagnoses of hemophilia A were heretofore obtained by using either intragenic factor VIII markers or linked cxtragcnic polymorphic markers. Postulating that the combined use of all the available intragenic and extragenic markers can render such diagnoses more frequently feasible and more reliable, we carried out ten first-trimester prenatal diagnoses in male fetuses at risk for hemophilia A by DNA analysis of chorionic villus employing in combination the intragenic Bcl I polymorphism and the St 14 (DXS 52) or DX 13 (DXS 15) extragenic probes. A diagnosis of hemophilia was obtained in three fetuses, with a diagnosis of normal fetus obtained in the remaining seven. Seven diagnoses are confirmed by factor VIII assays carried out at the time of abortion, in the mid-Trimester or at birth. A factor VIII probe recognizing Bcl I polymorphism was useful in 4 of 6 diagnoses; St 14, in 5 of 6; and DX 13 in 3 of 5. In two cases, St 14 was the only useful probe for diagnosis. Even though no recombination between extragenic probes and factor VIII gene was detected in this study, when only extragenic markers were informative we advised diagnostic confirmation on fetal plasma obtained by fetoscopy. Hence, first-trimester prenatal diagnosis of hemophilia A is feasible for the great majority of fetuses at risk through combined use of all the available intragenic and extragenic probes, providing key family members are available.

CARRIER DETECTION OF HEMOPHILIA A BY DNA ANALYSIS IN AFFECTED JAPANESE FAMILIES

1987 ◽  
Author(s):  
N Suzuki ◽  
A Iizuka ◽  
T Nagao ◽  
Y Nakahori ◽  
M Yamada ◽  
...  
Keyword(s):  
Factor Viii ◽  
Information Content ◽  
Japanese Population ◽  
Dna Analysis ◽  
Hemophilia A ◽  
Caucasian Population ◽  
Dna Probe ◽  
Carrier Detection ◽  
Dna Fragments ◽  
Factor Viii Gene

Several DNA probes have been isolated to detect Factor VIII gene and a DNA segment which locates veryclose to the gene. They have been successfully used to detect carriers and patients of hemophilia A.We analyzed DNA samples of Japanese population to see whether these probesare also useful for carrier detection of hemophilia A in affected Japanese families, since the size and frequency of allelic fragments detected by a DNA probe are sometimes different in various ethnic groups.A probe of St14 (DXS52) is thought to be one of the best probes for such analysis in Caucasian population because it detects very polymorphic DNA fragments containing a minisatellite. When Taq I digests of Japanese DNA samples were hybridized with Stl4, several DNA fragments with a range from 1.7 kb to 5-5 kb were detected, where .at least 6 fragments were polymorphic. A notable difference between Japanese and Caucasian was that a band of 5-5 kb was variable in Japanese while it was constant in Caucasian. We have so far detected 10 alleles, and about 60% of Japanese women were heterozygous. Using these informationsabout Japanese population, we could detect carriers in several families. Other RFLPs data are necessary to increase information content. Similar studies arein progress using different probes i.e. an extragenic probe ; DX13/Bgl II, and two intragenic probes ; exon 14-26/Bcl I and exon 26/Bgl I. We thank Mandel J.L., Strasbourg, Davies K., Oxford and Genetics Institute, Cambridge for probes.

scholarly journals HEMOPHILIA A: EXPERIENCE WITH PRENATAL DIAGNOSIS AND CARRIER DETECTION USING DNA ANALYSIS

1987 ◽  
Vol 21 (4) ◽  
pp. 293A-293A
Author(s):  
D G Phillips ◽  
S E Antonarakis ◽  
H H Kazarian
Keyword(s):  
Prenatal Diagnosis ◽  
Dna Analysis ◽  
Hemophilia A ◽  
Carrier Detection

Prenatal Diagnosis and Carrier Detection of Hemophilia A

2015 ◽  
pp. 84-87
Author(s):  
Maurizio Sampietro ◽  
Elisabetta Sacchi ◽  
Anna Maria Randi ◽  
Luigina Tagliavacca ◽  
Caterina Stefanile ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Hemophilia A ◽  
Carrier Detection

THE RELATIVE EFFICACY OF GENETIC ANALYSIS AND COAGULATION TESTING IN THE DIAGNOSIS OF CARRIERS OF HEMOPHILIA A

1987 ◽  
Author(s):  
D Lillicrap ◽  
A R Giles ◽  
J J A Holden ◽  
B N White
Keyword(s):  
Factor Viii ◽  
Gene Deletion ◽  
Hemophilia A ◽  
Fragment Length Polymorphism ◽  
Genetic Diagnosis ◽  
Prior History ◽  
Carrier Status ◽  
Factor Viii Gene ◽  
Coagulation Testing ◽  
History Of

This study has assessed the relative benefits of restriction fragment length polymorphism (RFLP) linkage and coagulation testing in the diagnosis of carriers of hemophilia A. 221 samples from 55 families have been studied for intragenic and flanking RFLPs. All samples were tested for the Factor VIII intragenic Bell RFLP and for the flanking marker St 14. 83% of obligate carrier females were heterozygous at oneor both of these two polymorphicsites. However, only38% of these women were heterozygous at the intragenic site and might safely be offered prenatal diagnosis using this marker for the hemophilia mutation. Carrier diagnosis was obtained in 52% of 81 potential carriers tested. Diagnosis wasbased on intragenic RFLP information in only 48% of these cases. Genetic diagnosis was possible in 27 atrisk women from families with no prior history of hemophilia. Four of these women were diagnosed as carriers on the basis of a gross Factor VIII gene deletion and the remaining 23 women were identified as non-carriers by the Bell (11) and Stl4 (12) RFLP data. 39 women remained undiagnosed after gene analysis studies. 23 of these women were female relatives of sporadic hemophiliacs and thus RFLP segregation analysis was inappropriate. A further 9 potential carriers were undiagnosed because of homozygosity in key individuals in their families. In 31 potential carriers we have quantitated Factor VIII:C (one stage assay) and vWf:Ag (Laurell and ELISA) and derived probabilities for carrier status. In 3 women there was conflicting genetic and coagulation data. Meanwhile, in 12 undiagnosed women from sporadic families, carrier diagnostic probabilities of > 0.9 were obtained. These studies indicate that optimal carrier detection for hemophilia A requires more intragenic and closely linked RFLPs and the continuance of coagulation testing to assist women from sporadic families.

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