Two New Nonsense Mutations in Type Ia Antithrombin III Deficiency at Leu 140 and Arg 197

Akira Tomonari; Hiroyuki Iwahana; Katsuhiko Yoshimoto; Toshio Shigekiyo; Shiro Saito; Mitsuo Itakura

doi:10.1055/s-0038-1646296

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 68(04): 455-459
DOI: 10.1055/s-0038-1646296

Original Article

Schattauer GmbH Stuttgart

Two New Nonsense Mutations in Type Ia Antithrombin III Deficiency at Leu 140 and Arg 197

Akira Tomonari

The First Department of Internal Medicine, The University of Tokushima, Japan

,

Hiroyuki Iwahana

¹The Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan

,

Katsuhiko Yoshimoto

¹The Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan

,

Toshio Shigekiyo

The First Department of Internal Medicine, The University of Tokushima, Japan

,

Shiro Saito

The First Department of Internal Medicine, The University of Tokushima, Japan

,

Mitsuo Itakura

¹The Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan

› Author Affiliations

Abstract

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Summary

Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, the molecular basis of hereditary type la antithrombin III (AT III) deficiency was disclosed in two families. One mutation was a change from T to A in the codon of TTA for Leu 140 forming a stop codon of TAA, which was confirmed by mutated primer-mediated PCR-HindIII digestion. The application of this method demonstrated that all four affected members had the mutant allele in a heterozygous state and that none of unaffected subjects had this mutation. Another mutation in the second family was a change from C to T in the codon of CGA for Arg 197 also forming a stop codon of TGA, which was confirmed by PCR-HaeIII digestion. Based on these, it was concluded that the two new nonsense mutations in the AT III gene in a heterozygous state are the molecular basis of hereditary type Ia AT III deficiency.

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References

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