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.
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