Three Distinct Point Mutations in the Factor IX Gene of Three Japanese CRM+ Hemophilia B Patients (Factor IX BMNagoya 2, Factor IX Nagoya 3 and 4)

Motohiro Hamaguchi; Tadashi Matsushita; Mitsune Tanimoto; Isao Tekahashi; Kohji Yamamoto; Isamu Sugiura; Junki Takamatsu; Kanji Ogata; Tadashi Kamiya; Hidehiko Saito

doi:10.1055/s-0038-1648182

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1991; 65(05): 514-520
DOI: 10.1055/s-0038-1648182

Original Article

Schattauer GmbH Stuttgart

Three Distinct Point Mutations in the Factor IX Gene of Three Japanese CRM⁺ Hemophilia B Patients (Factor IX B_MNagoya 2, Factor IX Nagoya 3 and 4)

Motohiro Hamaguchi

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

,

Tadashi Matsushita

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

,

Mitsune Tanimoto

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

,

Isao Tekahashi

^*The Aichi Juridical Foundation of Blood Disease Research, Nagoya, Japan

,

Kohji Yamamoto

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

,

Isamu Sugiura

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

,

Junki Takamatsu

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

,

Kanji Ogata

^**The Aichi-ken Shokuin Hospital, Naka-ku, Nagoya, Japan

,

Tadashi Kamiya

^***The Aichi Red Cross Blood Center, Seto, Aichi, Japan

,

Hidehiko Saito

The First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

› Institutsangaben

Abstract

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Summary

Enzymatic DNA amplification and complete sequence analysis were used to investigate human factor IX coding sequences in three CRM⁺ hemophilia B patients. In a patient with severe hemophilia B and a markedly prolonged ox-brain prothrombin time, a C to T transition in exon VI changed the codon for Argl80 to Trp (factor IX B_MNagoya 2). This mutation would impair the cleavage by factor XIa required for activation of the zymogen. In a patient with mild hemophilia B, a G to A transition in exon VI changed the codon for Argl45 to His (factor IX Nagoya 3). This substitution also would be predicted to preclude the cleavage of factor IX by factor XIa at this peptide bond (Argl45-Alal46). Furthermore, this point mutation creates a new NlaIII restriction site which provides a quick and reliable method for carrier detection in the affected family members. A patient with severe hemophilia B (factor IX Nagoya 4) had a G to A transition in exon II changing the codon for Glu21 to Lys. This novel point mutation is assumed to impair the function of factor IX by disrupting the calcium binding of factor IX.

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Referenzen

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