Molecular and genetic analysis of a compound heterozygote for dysprothrombinemia of prothrombin Tokushima and hypoprothrombinemia
- Univ. of Tokushima (Japan)
The molecular and genetic basis of a compound heterozygote for dys- and hypoprothrombinemia was analyzed. Abnormal nucleotide sequences of the human prothrombin gene were screened by PCR-single-strand conformation polymorphism (PCR-SSCP) with endonuclease digestion and mutated primer-mediated PCR-RFLP. A single nucleotide substitution responsible for dysprothrombinemia of prothrombin Tokushima was detected, as were three polymorphisms. The mutation for hypoprothrombinemia was detected by PCR-single-strand conformation polymorphism (PCR-SSCP) with endonuclease digestion in exon 6, near MboII-RFLP and NcoI-RFLP. Sequencing of PCR-amplified genomic DNA revealed a single base insertion of thymine (T) at position 4177. The resulting frameshift mutation caused both an altered amino acid sequence from codon 114 and a premature termination codon (i.e., TGA) at codon 174 in exon 7. Because exon 7 encodes the kringle 2 domain preceding the thrombin sequence, this frameshift leads to the null prothrombin phenotype. The inheritance of the hypoprothrombinemia gene from the father to the proband was proved by PCR-SSCP with endonuclease digestion and mutated primer-mediated PCR-RFLP. 30 refs., 7 figs., 1 tab.
- OSTI ID:
- 6707397
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 51:6; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AMINO ACID SEQUENCE
MUTATIONS
PROTHROMBIN
METABOLIC DISEASES
DNA
DNA SEQUENCING
GENES
PHENOTYPE
RFLPS
THROMBIN
THYMINE
AZINES
BLOOD COAGULATION FACTORS
COAGULANTS
DISEASES
DRUGS
ENZYMES
HEMATOLOGIC AGENTS
HEMOSTATICS
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
MOLECULAR STRUCTURE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HYDROLASES
PROTEINS
PYRIMIDINES
SERINE PROTEINASES
STRUCTURAL CHEMICAL ANALYSIS
URACILS
550400* - Genetics