Molecular and genetic analysis of a compound heterozygote for dysprothrombinemia of prothrombin Tokushima and hypoprothrombinemia

Journal Article · Tue Dec 01 04:00:00 EST 1992 · American Journal of Human Genetics; (United States)

OSTI ID:6707397

Iwahana, Hiroyuki; Yoshimoto, Katsuhiko; Shigekiyo, Toshio; Shirakami, Akira; Saito, Shiro; Itakura, Mitsuo ^[1]

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1. 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), Journal Name: American Journal of Human Genetics; (United States) Vol. 51:6; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
AZINES
BLOOD COAGULATION FACTORS
COAGULANTS
DISEASES
DNA
DNA SEQUENCING
DRUGS
ENZYMES
GENES
HEMATOLOGIC AGENTS
HEMOSTATICS
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
METABOLIC DISEASES
MOLECULAR STRUCTURE
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HYDROLASES
PHENOTYPE
PROTEINS
PROTHROMBIN
PYRIMIDINES
RFLPS
SERINE PROTEINASES
STRUCTURAL CHEMICAL ANALYSIS
THROMBIN
THYMINE
URACILS