Biochemical activity and gene analysis of inherited protein C and antithrombin deficiency in two Chinese pedigrees / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>We identified the gene mutations in two Chinese pedigree of type I hereditary protein C deficiency and type I hereditary antithrombin deficiency.</p><p><b>METHODS</b>The plasma level of protein C activity (PCA), protein C antigen (PCAg), protein S activity, antithrombin activity (ATA) and antithrombin antigen (ATAg) of propositi and two family members were detected using ELISA and chromogenic assay, respectively. All exons and intron-exon boundaries of protein C gene and antithrombin gene were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus.</p><p><b>RESULTS</b>The plasma PCA and PCAg of propositus 1 was 26% and 1.43 mg/dl, respectively. The PCAg and PCA of his father were normal. The decreased PCA level was seen in his mother and 4 of his maternal pedigree. PSA and ATA were all normal in pedigree 1 members. A C5498T heterozygous mutation in exon 3 of protein C gene, resulting in the substitution of Arg for Trp at the 15th amino acid, was identified in propositus 1 and 8 of his relatives. The plasma ATA and ATAg of propositus 2 was 48.6% and 10.4 mg/dl, respectively. The reduced ATA and ATAg levels were found in his father and 5 of paternal pedigree. PCA, PCAg and PSA were all in normal range. A heterozygous 13387-9G deletion in exon 6 of antithrombin gene was identified in propositus 2. This mutation introduced a frameshift and a premature stop at codon 426 and existed in 6 members of pedigree 2.</p><p><b>CONCLUSION</b>The C5498T heterozygous mutation in exon 3 of protein C gene, first reported in China, leads to type I hereditary protein C deficiency. The 13387-9G deletion, a novel mutation, can cause antithrombin deficiency and thrombosis.</p>