一个3型血管性血友病家系的基因及产前诊断  

Genetic and prenatal diagnosis of a pedigree affected with type 3 von Willebrand disease

作　　者：朱海燕[1] 季春燕[1] Zhu Haiyan Ji Chunyan(Center of Prenatal Diagnosis, Department of Gynecology and Obstetrics, Navy General Hospital, Beijing 100048, China)

机构地区：[1]中国人民解放军海军总医院妇产科产前诊断中心,北京100048

出　　处：《中华医学遗传学杂志》2017年第5期654-657,共4页Chinese Journal of Medical Genetics

摘　　要：目的对1例临床诊断为3型血管性血友病的患儿进行分子遗传学研究，明确致病突变，为再次妊娠的母亲进行产前诊断。方法提取基因组DNA，应用二代测序、Sanger测序对患儿VWF基因进行序列分析，对可疑致病突变位点，进行了家系成员及100份正常对照标本的验证。针对致病突变，羊膜腔穿刺采集羊水细胞，对胎儿进行产前基因诊断。结果序列分析检测到患儿VWF基因C．72874-1G〉A纯合突变，未见报道，经剪接位点预测软件分析，提示该剪接位点突变为致病突变，100份正常对照标本未见该突变；患儿父母及姐姐均为该突变携带者；产前诊断检测胎儿未遗传该突变，且VWF基因单体型与先证者不同。结论经过基因突变分析，发现了Ⅵ矿F基因的新突变，明确了患儿的致病突变及表型一基因型关系，确定了患儿及家系成员的基因型，成功为胎儿进行了产前诊断，积累了该类疾病的诊断经验。Objective To provide genetic and prenatal analysis for a pedigree affected with type 3 von Willebrand disease. Methods Next generation sequencing and Sanger sequencing of the VWF gene were carried out for the pedigree. Suscepted pathogenic mutation was verified among other members of the pedigree and 100 healthy controls. Prenatal diagnosis was performed on amniotic cells derived from the fetus. ResuLts A homozygous mutation c. 7287 ＋ 1G^A of the VWF gene was detected in the patient, which was predicted by bioinformatic analysis as a pathological splice site mutation. The parents and sister of the patient have all carried the same mutation. The mutation was not detected among the 100 healthy controls. Prenatal diagnosis confirmed that the fetus did not inherit the same mutation. Conclusion A novel mutation of the VWF gene was discovered, which correlated with the phenotype of the patient. Based on the discovery, prenatal diagnosis was provided for a fetus during subsequent pregnancy.

关 键 词：3型血管性血友病 VWF基因 基因诊断 产前诊断 

分 类 号：R440[医药卫生—诊断学] R554.1[医药卫生—临床医学]