A novel factor XII mutation, FXII R84P, causing factor XII deficiency in a patient with hereditary spastic paraplegia

Eri Matsuki, Yoshitaka Miyakawa, Shinichiro Okamoto

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Hereditary factor XII (FXII) deficiency is a clinically asymptomatic, autosomal recessive disorder. We have experienced a rare case of FXII deficiency in a patient previously diagnosed with hereditary spastic paraplegia (HSP). The patient had no major bleeding episodes and presented with a prolonged activated partial thromboplastin time (APTT) at hospital administration. Sequencing of the FXII gene revealed a novel missense mutation at exon 4 that substitutes arginine 84 to proline (R84P). To elucidate the molecular mechanism of FXII deficiency, wild-type and R84P mutant FXII cDNA were transiently expressed in CHO cells. We found that secretion but not synthesis of R84P mutant protein was markedly reduced compared to wild type. These results indicated that R84P mutation might impair the intracellular transport or secretion of FXII protein of the cells and could be a useful tool for the analysis of structure-function relationship and intracellular protein transport of FXII protein in the future.

Original languageEnglish
Pages (from-to)227-230
Number of pages4
JournalBlood Coagulation and Fibrinolysis
Volume22
Issue number3
DOIs
Publication statusPublished - 2011 Apr

Fingerprint

Factor XII Deficiency
Hereditary Spastic Paraplegia
Factor XII
Mutation
Hospital Administration
Partial Thromboplastin Time
CHO Cells
Protein Transport
Missense Mutation
Mutant Proteins
Proline
Arginine
Exons
Proteins
Complementary DNA
Hemorrhage
Genes

Keywords

  • Coagulopathy
  • factor XII
  • factor XII deficiency
  • hereditary spastic paraplegia

ASJC Scopus subject areas

  • Hematology

Cite this

A novel factor XII mutation, FXII R84P, causing factor XII deficiency in a patient with hereditary spastic paraplegia. / Matsuki, Eri; Miyakawa, Yoshitaka; Okamoto, Shinichiro.

In: Blood Coagulation and Fibrinolysis, Vol. 22, No. 3, 04.2011, p. 227-230.

Research output: Contribution to journalArticle

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