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CRM+ haemophilia A due to a missense mutation (372----Cys) at the internal heavy chain thrombin cleavage site.

Pattinson, JK, McVey, JH, Boon, M, Ajani, A and Tuddenham, EG (1990) CRM+ haemophilia A due to a missense mutation (372----Cys) at the internal heavy chain thrombin cleavage site. Br J Haematol, 75 (1). pp. 73-77.

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Abstract

We have used the polymerase chain reaction (PCR) and differential oligonucleotide melting to screen for mutations in selected CpG dinucleotides in the factor VIII genes of haemophilia A patients. By this means we have identified and confirmed by sequencing a novel point mutation in codon 372 (CGC) of the factor VIII gene of a moderately severe CRM+ haemophiliac. The first C of this codon has been substituted by T resulting in the non-conservative substitution of cysteine for arginine at an essential thrombin cleavage site in factor VIII. Analysis of three intragenic restriction fragment length polymorphisms was uninformative in the patient's family. However, DNA analysis for the specific mutation shows one sister and the patient's mother to be carriers, and the other sister to be normal. This DNA analysis confirmed the results of phenotype analysis by factor VIII coagulant to von Willebrand factor antigen ratios for the females at risk. The two carrier females had low factor VIII coagulant activity and excess VIII antigen as predicted but the non-carrier sister also had anomalously high VIII antigen in her plasma. When feasible, mutation specific DNA analysis is able to resolve the difficulties posed by variable phenotype data and unknown level of mutation in sporadic haemophilia A.

Item Type: Article
Authors :
NameEmailORCID
Pattinson, JKUNSPECIFIEDUNSPECIFIED
McVey, JHj.mcvey@surrey.ac.ukUNSPECIFIED
Boon, MUNSPECIFIEDUNSPECIFIED
Ajani, AUNSPECIFIEDUNSPECIFIED
Tuddenham, EGUNSPECIFIEDUNSPECIFIED
Date : May 1990
Uncontrolled Keywords : Base Sequence, DNA Mutational Analysis, Dinucleoside Phosphates, Factor VIII, Family, Female, Hemophilia A, Heterozygote Detection, Humans, Male, Molecular Sequence Data, Mutation, Pedigree, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Thrombin
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:16
Last Modified : 17 May 2017 14:48
URI: http://epubs.surrey.ac.uk/id/eprint/827101

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