摘要
目的对 1 例遗传性抗凝血酶(AT)缺陷症患者及其家系成员 AT 活性(AT:A)、AT 抗原含量(AT:Ag)进行检测及基因分析,探讨该遗传性 AT 缺陷症发病的分子机制。方法采用发色底物法和免疫比浊法分别检测先证者及其家系成员血浆 AT:A 和 AT:Ag,提取外周血基因组 DNA,PCR法扩增 AT 基因的全部7个外显子及侧翼序列,DNA 序列分析 AT 的基因异常。结果先证者 AT:A和 AT:Ag 分别为45%和97 mg/L,为Ⅰ型 AT 缺陷症。AT 基因外显子5区第9833位核苷酸发生杂合性 T→A突变,引起 Tyr363Stop(Y363X)无义突变。其他家系成员基因测序结果显示有4人(Ⅱ2、Ⅱ6、Ⅲ7、Ⅲ14)存在该突变。结论该家系为Ⅰ型遗传性 AT 缺陷症 AT 基因外显子5区杂合性9833 T→A无义突变引起 AT 缺陷,导致静脉血栓是该遗传性 AT 缺陷症的分子致病机制。该突变在国际上尚未见报道。
Objective To investigate the antithrombin （AT） activity （AT： A ） and AT antigen （AT： Ag） level in a Chinese family with type [ 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 oth- er 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.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2006年第9期598-601,共4页
Chinese Journal of Hematology
基金
2005年安徽省临床医学重点学科应用技术资助项目(05A018)
关键词
抗凝血酶缺陷症
遗传性
基因
突变
Antithrombin deficiency, hereditary
Gene
Mutation
