Molecular characterization of human factor XSan Antonio. Blood 1989 Oct;74(5):1486-90
Date
10/01/1989Pubmed ID
2790181Scopus ID
2-s2.0-0024744646 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
Enzymatic amplification technique was used to isolate all eight exons and sequences around the splice junctions, putative promoter, and polyadenylation sites of human factor X DNA from a patient with factor X deficiency. Two genetic changes in factor X have been observed in this patient. The patient is most likely a compound heterozygote since there is only 14% activity associated with factor X. A point mutation that resulted in the substitution of cysteine (TGC) for arginine (CGC) at amino acid 366 was found in exon VIII of one allele of the factor X gene. This mutation, which occurs in the catalytic domain, can affect the formation of a disulfide bridge and thus could result in a reduction in factor X activity. Sequencing all the regions revealed a second mutation: a deletion of one nucleotide (TCCT to TCT) in exon VII that would cause a frame shift at amino acid 272 followed by termination. We have also shown that the point mutation in exon VIII creates an ApaL1 restriction site and destroys the HinP1 site. Enzymatic DNA amplification followed by restriction digestion provides a quick, reliable, and sensitive method for carrier detection and antenatal diagnosis in affected kindreds. This is the first characterization of factor X deficiency at the molecular level. We propose to name this mutation Factor XSan Antonio.
Author List
Reddy SV, Zhou ZQ, Rao KJ, Scott JP, Watzke H, High KA, Jagadeeswaran PMESH terms used to index this publication - Major topics in bold
AllelesBase Sequence
DNA
Exons
Factor X
Factor X Deficiency
Female
Gene Amplification
Humans
Hypoprothrombinemias
Male
Molecular Sequence Data
Mutation
Promoter Regions, Genetic
RNA Splicing
Restriction Mapping
