[A novel mutation in antithrombin gene results in hereditary antithrombin deficiency].

ABSTRACT

OBJECTIVE: To investigate the antithrombin (AT) activity (AT A) and AT antigen (AT Ag) level in a Chinese family with type I antithrombin (AT) deficiency, and to explore the molecular mechanism of AT deficiency. METHODS: Immuno-nephelometry and chromogenic assay were used to detect the plasma level of AT A and AT Ag, respectively. Genomic DNA was isolated from the peripheral blood, and all the seven exons and exon-intron boundaries of AT gene were amplified by PCR and direct sequencing. RESULTS: The plasma levels of AT A and AT Ag of the proband were 45% and 97 mg/L, respectively, which led to a type I AT deficiency. A heterozygous T to A mutation was found at nucleotide 9833 in exon 5 resulting in a Tyr363Stop nonsense mutation. The sequencing results from the pedigree indicated that four other members also had this mutation. CONCLUSION: This heterozygous nonsense mutation of T9833A in exon 5 resulting in venous thrombosis is a novel genetic defect of hereditary AT deficiency, which has not been described before.