CARRIER DETECTION IN JAPANESE FAMILIES WITH HAEMOPHILIA A USING FACTOR VIII GENE PROBE(F8A) AND ST 14-1 PROBE

1987 ◽  
Author(s):  
M Nishino ◽  
T Nishimura ◽  
H Naka ◽  
S Mikami ◽  
A Yoshioka ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Dna Probe ◽  
Carrier Detection ◽  
Carrier Status ◽  
Gene Probe ◽  
Haemophilia A ◽  
Factor Viii Gene ◽  
X Chromosomes ◽  
The Family ◽  
The Relationship

Recently, the gene structure for human F.VIII protein was clarified, and F.VIII DNA probes have been used for carrier detection and prenatal diagnosis ofhaemophilia A. In order to make sure that the phenomena are universal, we have analysed the RFLPs of F.VIII gene in 16 Japanese families with haemophilia A, including a female haemophiliac case, using an intragenic F.VIII DNA probe(F8A) and an extragenic(linked) DNA probe(Stl4-1).The probe F8A revealed two variant bands after digestion by Bel I. Of normal 60 X chromosomes (females) examined, about 85% bore the 879-bp fragment and 15%the 1165-bp fragment. Five of sixteen mothers of hemophiliacs, definite carriers, were found to be heterozygous for Bel I polymorphism. Since the relationship between Bel I alleles and hemophilia gene has been identified in the 5 families in which the mothers were heterozygous, we could diagnose the carrier status of two women whose brothers are hemophiliacs. Onthe other hand, we could identify that one "haemophilic woman" with less than 10% of F.VIII:C was a carrier status when we analysed the Bel I alleles in theother members of the family.The probe DNA(ST 14-1) revealed seven variant bands ranging from 5.5 kb to 3.4 kb after digestion by Taq I. In 6 out of 16 families, the RFLPs of ST 14 locus were informative for carrier detection.From these data, it was concluded that the Bel I polymorphism of F.VIII gene and the Taq I polymorphism of ST 14 locus were informative for carrier detection in 8 out of 16 families with haemophilia A

scholarly journals Inversions in the factor VIII gene: improvement of carrier detection and prenatal diagnosis in Dutch haemophilia A families.

1995 ◽  
Vol 32 (4) ◽  
pp. 296-300 ◽  
Author(s):  
P P Deutz-Terlouw ◽  
M Losekoot ◽  
R Olmer ◽  
W C Pieneman ◽  
S de Vries-v d Weerd ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Factor Viii ◽  
Carrier Detection ◽  
Haemophilia A ◽  
Factor Viii Gene

scholarly journals Carrier detection in Japanese haemophilia a families using factor VIII gene probe (F8A) and the gene-linked ST 14-1 probe

1987 ◽  
Vol 32 (3) ◽  
pp. 237-245 ◽  
Author(s):  
Masato Nishino ◽  
Takuya Nishimura ◽  
Hiroyuki Naka ◽  
Sadaaki Mikami ◽  
Takashi Tokino ◽  
...  
Keyword(s):  
Factor Viii ◽  
Carrier Detection ◽  
Gene Probe ◽  
Haemophilia A ◽  
Factor Viii Gene

scholarly journals First trimester prenatal diagnosis of haemophilia a using factor VIII gene probe

1989 ◽  
Vol 34 (2) ◽  
pp. 135-141
Author(s):  
Akira Yoshioka ◽  
Hiroyuki Naka ◽  
Takuya Nishimura ◽  
Kuninori Kuze ◽  
Ichiro Tanaka ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Factor Viii ◽  
First Trimester ◽  
Gene Probe ◽  
Haemophilia A ◽  
Factor Viii Gene

ANTENATAL DIAGNOSIS AND CARRIER DETECTION OF HAEMOPHILIA A USING FACTOR VIII GENE PROBE

The Lancet ◽  
1985 ◽  
Vol 325 (8437) ◽  
pp. 1093-1094 ◽  
Author(s):  
J. Gitschier ◽  
R.M. Lawn ◽  
F. Rotblat ◽  
E. Goldman ◽  
E.G.D. Tuddenham
Keyword(s):  
Factor Viii ◽  
Antenatal Diagnosis ◽  
Carrier Detection ◽  
Gene Probe ◽  
Haemophilia A ◽  
Factor Viii Gene

Carrier detection in haemophilia A by direct analysis of factor VIII gene lesions

1991 ◽  
Vol 87 (1) ◽  
pp. 99-100
Author(s):  
David S. Millar ◽  
Peter J. Green ◽  
Barbara Zoll ◽  
Vijay V. Kakkar ◽  
David N. Cooper
Keyword(s):  
Factor Viii ◽  
Direct Analysis ◽  
Carrier Detection ◽  
Haemophilia A ◽  
Factor Viii Gene

Use of CSGE, TspRI- RFLP and Western Blot in Carrier Detection in an Indian Family with Type I Glanzmann Thrombasthenia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3975-3975 ◽  
Author(s):  
Meganathan Kannan ◽  
Firdos Ahmad ◽  
Rajive Kumar ◽  
Ved P. Choudhry ◽  
Renu Saxena
Keyword(s):  
Flow Cytometry ◽  
Western Blot ◽  
Family Members ◽  
Carrier Detection ◽  
Carrier Status ◽  
Type I ◽  
Restriction Digestion ◽  
Glanzmann Thrombasthenia ◽  
The Family ◽  
Abnormal Band

Abstract Glanzmann Thrombasthenia (GT) is an inherited, autosomal recessive, bleeding disorder which is characterized by absent/reduced platelet Glycoprotein IIb/IIIa. The sub classification of GT into Types I, II and III is based on the levels of GPIIb/IIIa by flow cytometry. Type I is the most severe form of GT and is found to be most common in north Indian population. Since not much study is available on carrier detection based on western blot analysis, it is suggested to confirm the defect in carriers by molecular diagnosis. Here we present a carrier status using TspRI in a family with Glanzmann Thrombasthenia patient. Glanzmann Thrombasthenia was diagnosed in a patient with bleeding manifestations accompanied by absent platelet aggregation, secondary to ADP, ADR, Arachidonic acid and collagen. The patient was sub typed as Type I based on flow cytometry analysis as he had absent GPIIb/IIIa. Patient’s DNA was analyzed for mutation in both the gpIIb and gpIIIa genes by CSGE, followed by sequencing. The patient was found to have mutation, CTG>CCG at exon 12 of GPIIb gene. The mutation caused amino acid change from Leu to Pro in the GPIIb protein. The same mutation was looked for in all the family members (Both parents and two siblings) using CSGE and by TspRI- RFLP analysis. Both the parents and siblings were heterozygous for this mutation, where as patient was homozygous (Fig 1). As this mutation is not present in the normal individuals and is not reported earlier, this considers being a novel mutation. Presence of abnormal protein in the family members was revealed by western blot analysis for GPIIb (Fig 2). The same mutation is being looked for in more number of patients with Glanzmann Thrombasthenia using TspRI- RFLP. So far, a total of two out of 25 GT patients found to carry this mutation. It is possible that abnormal GPIIb protein by western blot in family members may reflect their carrier status. It is also postulated that western blot and CSGE of GPIIb and IIIa in parents/siblings may detect carrier status in Glanzmann Thrombasthenia. Fig 1: Carrier detection by restriction digestion using TspRI Fig 1:. Carrier detection by restriction digestion using TspRI Fig 2: Immunoblot followed by chemiluminescent detection shows absent/reduced protein in patient and abnormal band pattern in the family members Fig 2:. Immunoblot followed by chemiluminescent detection shows absent/reduced protein in patient and abnormal band pattern in the family members

PRENATAL DIAGNOSIS OF HAEMOPHILIA A BY FACTOR VIII GENE ANALYSIS

The Lancet ◽  
1985 ◽  
Vol 325 (8443) ◽  
pp. 1407-1409 ◽  
Author(s):  
StylianosE Antonarakis ◽  
KarenL Copeland ◽  
RobertJ Carpenter ◽  
CarlA Carta ◽  
LeonW Hoyer ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Factor Viii ◽  
Gene Analysis ◽  
Haemophilia A ◽  
Factor Viii Gene

Haemophilia A in a Female: Study of a Family Using Intragenic and Extragenic Restriction Site Polymorphisms

1988 ◽  
Vol 60 (01) ◽  
pp. 102-106 ◽  
Author(s):  
G Piétu ◽  
N Thomas-Maison ◽  
P Sié ◽  
M J Larrieu ◽  
D Meyer
Keyword(s):  
Cdna Probe ◽  
Normal Karyotype ◽  
Restriction Enzymes ◽  
Carrier Status ◽  
Haemophilia A ◽  
Bleeding Tendency ◽  
Excessive Bleeding ◽  
Length Polymorphisms ◽  
The Family ◽  
Restriction Site Polymorphisms

SummaryRestriction fragment length polymorphisms(RFLPs) were studied in a large Algerian family which includes 6 haemophiliacs and a previously described case of female haemophilia A. The female propositus is 66 years old with a normal karyotype. Her parents are first cousins. Her 3 sons are haemophiliacs and her 3 daughters with affected children are obligate carriers. The proband has an excessive bleeding tendency and markedly reduced levels of F. VIII (VIII C 0.03 U/ml, VIII Ag 0.01 U/ml) with elevated vWF Ag (2.30 U/ml), similar to the levels observed in affected males from the family. Four RFLPs can be identified by Southern blotting after digesting genomic DNA with the restriction enzymes Bcl I, Bgl I, Kpn I/Xba I and Taq I and hybridization with a 647 bp Stu I/Sca I F. VIII genomic probe, a 1.8 Kb EcoRI F. VIII cDNA probe, a 1.0 Kb EcoRI/Sst I fragment of intron 22 and the extragenic probe ST 14, respectively. With these four RFLPS, the propositus was found to be homozygous for the alleles segregating in this family with the abnormal X-chromosome. The carrier status was proven in a granddaughter and excluded in another. In conclusion, this RFLP linkage analysis is another argument to suggest that the propositus, a rare case of female haemophilia, is homozygous for the abnormal gene.

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