一个遗传性血管性水肿家系的临床及基因研究  

Clinical and genetic studies of a family with hereditary angioedema

作　　者：贾薇 索利敏 范林静[2] 董佩 李通 冀永进 薛金梅[2] 安云芳[2] 赵长青[2] 张亚茜[3] 段建雄 Jia Wei;Suo Limin;Fan Linjing;Dong Pei;Li Tong;Ji Yongjin;Xue Jinmei;An Yunfang;Zhao Changqing;Zhang Yaxi;Duan Jianxiong(Department of Biochemistry and Molecular Biology,Basic Medical College,Shanxi Medical University,Taiyuan 030001,China;Department of Otorhinolaryngology Head Neck Surgery,the Second Hospital,Shanxi Medical University,Key Research Laboratory of Airway Neuroimmunology,Taiyuan 030001,China;Shanxi Guoxin Caregeno Medical Laboratory,Taiyuan 030001,China;Shanghai Lanwei Medical Laboratory Co.,LTD.,Shanghai 200335,China)

机构地区：[1]山西医科大学基础医学院生物化学与分子生物学教研室,太原030001 [2]山西医科大学第二医院耳鼻咽喉头颈外科山西省气道炎性疾病神经免疫(重点培育)实验室,太原030001 [3]山西国信凯尔医学检验所,太原030001 [4]上海兰卫医学检验所股份有限公司,上海200335

出　　处：《中华耳鼻咽喉头颈外科杂志》2022年第8期980-985,共6页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：山西省重点研发计划项目(201803D31122);山西省留学人员科技活动择优资助项目(2019-39)。

摘　　要：目的确诊一个遗传性血管性水肿患者大家系,并对其遗传方式和基因位点进行研究。方法回顾性分析2021年8月至2022年2月于山西医科大学第二医院耳鼻咽喉头颈外科接受病史采集、实验室检查的1名先证者(女,48岁)及12名家族内患病成员与未患病成员的临床资料[其中男7名,女5名,年龄12~78(中位24)岁],在明确诊断的同时绘制家系图。用全外显子测序技术检测先证者的遗传序列,并对其家庭成员进行验证,绘制突变的遗传系谱。结果该家系遗传方式为常染色体显性遗传,经实验室检查确诊该家系8名成员患有遗传性血管性水肿,其中Ⅰ型7例,Ⅱ型1例。分别对2种表型的2名患者进行全外显子测序分析,发现均携带同1个致病突变位点,为c.890-2A>G。对家系成员进行一代测序验证,结果发现,此家系中曾有水肿史的成员均含有此突变位点,而先证者无水肿史的弟弟无此突变。结论该遗传性血管性水肿家系可同时出现Ⅰ型和Ⅱ型两种表型,SERPING1基因c.890-2A>G突变是导致该家系患者发病的原因。Objective To diagnose a large family of patients with hereditary angioedema,and to study its inheritance pattern and gene locus.Methods A retrospective analysis was carried out from August 2021 to February 2022 in a proband(female,48 years old)and 12 family members who underwent medical history collection and laboratory examinations in the Department of Otorhinolaryngology and Head and Neck Surgery,the Second Hospital of Shanxi Medical University.The clinical data of members and non-affected members[including 7 males and 5 females,aged 12-78(median 24)years old],were drawn a family map while confirming the diagnosis.Whole exome sequencing technology was used to detect the genetic sequence of the proband and to verify its family members to map the genetic pedigree of the mutation.Results The inheritance pattern of the family was autosomal dominant,and 8 members of the family were diagnosed with hereditary angioedema by laboratory examination,including 7 cases of type I and 1 case of typeⅡ.Whole exome sequencing analysis was performed on 2 patients with 2 phenotypes,and it was found that they both carried the same pathogenic mutation locus,which was c.890-2A>G.The family members were verified by next-generation sequencing,and it was found that all members of the family who had a history of edema contained this mutation site,while the younger brother of the proband who had no history of edema did not have this mutation.Conclusion Both typeⅠand typeⅡphenotypes are present in this hereditary angioedema family,and the mutation of SERPING1 gene c.890-2A>G causes the onset of each patient in this family.

关 键 词：遗传性血管性水肿 C1酯酶抑制剂 全外显子测序 SERPING1基因 

分 类 号：R442.5[医药卫生—诊断学]