摘要
目的鉴定一个甲型血友病家系致病基因突变,并对该家系提供产前诊断指导。方法对该家系先证者F8基因进行一代测序、多重连接探针扩增技术及22号内含子倒位检测,对家系中有血缘关系的成员通过一代测序进行基因突变验证,再分析家系各成员疾病表型和基因突变是否共分离,再对致病基因突变进行产前诊断,并在胎儿出生半年后进行相关凝血功能检测。结果在先证者及另一男性患者中鉴定出F8基因新突变c.529T>C(p.Tyr177His),且未发现其他点突变、插入缺失及22号内含子倒位存在。在该家系其他成员中验证此突变,符合疾病表型与基因突变共分离。为该家系中2名女性孕妇(携带者)进行产前诊断,胎儿均未携带该基因突变,出生半年左右凝血功能检测结果均正常。结论F8基因新突变c.529T>C为该甲型血友病家系的致病性突变。
Objective To identify the pathogenic genetic variant in a Chinese hemophilia A(HA)family and to provide prenatal diagnostic for the family members.Methods We performed sanger sequencing,MLPA(multiplex ligation-dependent probe amplification)and 22 intron inversion PCR test on F 8 gene for the probands of the family,and used sanger sequencing for the other related family members to check whether clinical phenotype was co-isolated with the variant.And then we proceed prenatal diagnosis on the pathogenic mutaion for two carried pregant women in this HA family.Results A novel variant of F 8 gene c.529T>C(p.Tyr177His)was identified from the proband,and no other missense variations,small insertions and deletions or inversion of the 22th intron were found.The result of the variant testing in another affected male and other family members confirmed the patients'phenotype was co-separated with the variant too.Prenatal diagnosis was conducted for two female carriers in this HA family,and the neonatal coagulation function testing was normal.Conclusion Gene F 8 mutation c.529T>C was a novel variation and identified as the pathogenic variant in this HA family.
作者
赵强
潘焯仪
吴欣新
张妙莲
冼诗瑶
吴海涛
ZHAO Qiang;PAN Zhuoyi;WU Xinxin;ZHANG Miaolian;XIAN Shiyao;WU Haitao(Department of Obstetrics and Gynecology,Jiangmen Central Hospital,The Affiliated Jiangmen Hospital of Sun Yat-Sen University,Jiangmen 529030,China)
出处
《福建医科大学学报》
2021年第1期57-61,共5页
Journal of Fujian Medical University
基金
广东省自然科学基金(2018A030310050)。
关键词
甲型血友病
F8
产前诊断
新突变
hemophilia A
F8
prenatal diagnosis
novel mutation
coagulation
