Genetic analysis of hereditary factor X deficiency in a French patient of Sri Lankan ancestry: In vitro expression study identified Gly366Ser substitution as the molecular basis of the dysfunctional factor X

Ikuko Isshiki, Remi Favier, Takanori Moriki, Toshihiro Uchida, Hiroaki Ishihara, Patrick Van Dreden, Mitsuru Murata, Yasuo Ikeda

研究成果: Article査読

10 被引用数 (Scopus)

抄録

We investigated a new family with cross-reactive material-positive factor X (FX) deficiency. The proband was an 11-year-old French girl from Sri Lanka with a tendency towards severe bleeding. The FX antigen level was 67%, although the activity with extrinsic pathway was 1 U/dl. The complete nucleotide sequences of all exons and exon/ intron junctions of the patient's genomic DNA revealed a homozygous G → A substitution in exon 8, which would result in replacement of Gly366 with Ser. The proband is the first reported case of homozygote for the FX Gly366Ser mutation. Heterozygosity for Gly366Ser substitution was previously reported in a Japanese patient (FX Nagoya 2). We studied the functional consequences by expressing mutant FX Gly366Ser protein in HEK293 cells. FX Gly366Ser was secreted into the culture media at levels similar to wild-type FX; however, mutant FX activities were only 0.04, 1.05, and 0.75% of wild-type FX upon activation by the extrinsic system, the intrinsic system, and Russell's viper venom, respectively. Moreover, the activity of FX Gly366Ser was undetectable when analyzed with chromogenic-activated FX and thrombin generation assays. These data suggest that the Gly366Ser substitution would cause a major defect in function of the FX molecule.

本文言語English
ページ(範囲)9-16
ページ数8
ジャーナルBlood Coagulation and Fibrinolysis
16
1
DOI
出版ステータスPublished - 2005 1 1

ASJC Scopus subject areas

  • 血液学

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