Identification of two novel mutations in ADAMTS13 gene in a patient with hereditary thrombotic thrombocytopenic purpura / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the gene mutations of ADAMTS13 in a highly suspected hereditary thrombocytopenic purpura (TTP) patient, and then make a progressive diagnosis and adjust the plan of therapy.</p><p><b>METHODS</b>ADAMTS13 activity and inhibitor were determined by residual-collagen binding assay during several episodes. Genomic DNA extracted from the proband's peripheral blood was used for amplification of 29 exons and exon/intron boundaries of ADAMTS13 by PCR. The PCR products were screened by direct sequencing and the gene alterations were further confirmed by direct sequencing in her family members.</p><p><b>RESULT</b>The activity of the proband's ADAMTS13 was significantly reduced while no inhibitor was found. Two novel missense mutations were found in the TSPI repeated motif domain of ADAMTS13. In both mutations, thymine substituted for cytidine, resulting in the substitution of leucine for serine in nt 2708, exon 21 (codon S903L), and tryptophan for arginine in nt 3283, exon 25(codon R1095W). These two mutations were revealed as each heterozygote in the proband's parents.</p><p><b>CONCLUSION</b>The deficiency of ADAMTS13 caused by two homozygote missense mutations might be responsible for episode of this TTP patient.</p>