A recurrent deletion in the antithrombin gene, AT106-108(-6 bp), identified by DNA heteroduplex detection

Journal Article · Thu Apr 01 00:00:00 EST 1993 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1993.1184· OSTI ID:6287848

Olds, R J; Thein, S L ^[1]; Lane, D A ^[2]; Beresford, C H; Hughes, P M ^[3]; Abildgaard, U ^[4]

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1. John Radcliffe Hospital, Oxford (United Kingdom)
2. Charing Cross and Westminster Medical School, London (United Kingdom)
3. Univ. of Otago Medical School, Dunedin (New Zealand)
4. Aker Hospital, Oslo (Norway)

Antithrombin is the major physiological inhibitor of the activated serine proteinases of the coagulation system. Hereditary deficiency of the inhibitor is transmitted in an autosomal dominant pattern and is associated with a risk of venous thromboembotic disease in affected individuals. In the classical form of deficiency, type Ia, plasma antithrombin is reduced to approximately half normal in both functional and immunological assays. The authors report here the identification of a recurrent mutation as the basis for type Ia deficiency in two independent kindreds, one from New Zealand and the other from Norway, and demonstrate the utility of DNA heteroduplex detection as a method for screening for the presence of mutations. Standard functional and immunological assays for plasma antithrombin showed levels of approximately half normal in several members of both kindreds, consistent with the classification as type Ia deficiency. The plasma of the proband from the Norwegian kindred was examined by crossed immunoelectrophoresis, in the presence or absence of heparin in the first dimension, and an abnormal component that may have represented a variant form of the inhibitor was not identified. In both families affected members have had episodes of venous thrombosis, although some carriers of the abnormal allele, as confirmed in the current study, so far have not had clinical thrombotic disease. 7 refs., 2 figs.

• OSTI ID: 6287848
• Journal Information: Genomics; (United States), Vol. 16:1; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ENZYME INHIBITORS
GENE MUTATIONS
SERINE PROTEINASES
INHIBITION
THROMBOSIS
BLOOD COAGULATION
DNA SEQUENCING
RFLPS
THROMBIN
VASCULAR DISEASES
BLOOD COAGULATION FACTORS
CARDIOVASCULAR DISEASES
COAGULANTS
DISEASES
DRUGS
ENZYMES
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
MUTATIONS
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics