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


CONCLUSIONS
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.
Zhang
Fu-Hua
FH
Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, China.
Ding
Qiu-Lan
QL
Wu
Jing-Sheng
JS
Zhou
Rong-Fu
RF
Wang
Xue-Feng
XF
Xu
Xiu-Cai
XC
D020152:Antithrombin III Deficiency / Q000235:genetics*; D000991:Antithrombins / Q000235:genetics*; D001780:Blood Coagulation Tests; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D000991:Antithrombins