DNA Sequence Analysis of Protein S Deficiency-Identification of Four Point Mutations in Twelve Japanese Subjects

Takayuki Iwaki; Tadashi Mastushita; Takao Kobayashi; Yukako Yamamoto; Yuka Nomura; Kazuo Kagami; Takayuki Nakayama; Isamu Sugiura; Tetsuhito Kojima; Junki Takamatsu; Naohiro Kanayama; Hidehiko Saito

doi:10.1055/s-2001-14075

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2001; 27(2): 155-160
DOI: 10.1055/s-2001-14075

DNA Sequence Analysis of Protein S Deficiency-Identification of Four Point Mutations in Twelve Japanese Subjects

Takayuki Iwaki¹ , Tadashi Mastushita² , Takao Kobayashi¹ , Yukako Yamamoto³ , Yuka Nomura² , Kazuo Kagami² , Takayuki Nakayama² , Isamu Sugiura⁴ , Tetsuhito Kojima⁵ , Junki Takamatsu³ , Naohiro Kanayama¹ , Hidehiko Saito² ⁶

¹Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan
²First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
³Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan
⁴Toyohashi City Hospital, Toyohashi, Japan
⁵Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan
⁶Aichi Blood Disease Research Foundation, Nagoya, Japan

Abstract

ABSTRACT

The molecular basis for the hereditary type I protein S (PS) deficiency was investigated. DNA sequence analysis of 12 patients with PS deficiency in Japan identified four point mutations and three of them were novel. Nonsense mutations found in two unrelated patients resulted in termination of the PS polypeptide chains at Gln 238 and Lys 392, respectively. Two novel missense mutations were also found in two other patients substituting Asp 202 for Asn and Leu 298 for Pro, respectively. Comparison of the PS amino acid sequences from several mammalians indicated that Asp 202 and Leu 298 were preserved and thus appeared to be responsible for the pathogenesis of PS deficiency.

KEYWORD

Protein S deficiency - thrombosis - genetic diagnosis - polymerase chain reaction - mutation

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Referenzen

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