遗传性血管性水肿1家系C1抑制物基因变异分析  

Variation Analysis of C1 Inhibitor Gene in a Family with Hereditary Angioedema

作　　者：杜文锦 杨科 李聪敏 张秋兴 林香花 刘慧芳 张文超 郭维丽 孟照吉 王东海 刘丹 王思勤 DU Wenjin;YANG Ke;LI Congmin;ZHANG Qiuxing;LIN Xianghua;LIU Huifang;ZHANG Wenchao;GUO Weili;MENG Zhaoji;WANG Donghai;LIU Dan;WANG Siqin(Department of Allergy,Henan Provincial People′s Hospital,People′s Hospital of Zhengzhou University,People′s Hospital of Henan University,Zhengzhou 450003,China;Medical Genetics Institute,Henan Provincial People′s Hospital,Zhengzhou University People′s Hospital,People′s Hospital of Henan University,Henan Key Laboratory of Genetic Diseases and Functional Genomics,Zhengzhou 450003,China;Department of Nephrology,Zhumadian Central Hospital,Zhumadian 463000,China)

机构地区：[1]河南省人民医院过敏反应科,郑州大学人民医院,河南大学人民医院,河南郑州450003 [2]河南省人民医院医学遗传研究所,河南省遗传性疾病功能基因组重点实验室,郑州大学人民医院,河南大学人民医院,河南郑州450003 [3]驻马店中心医院肾内科,河南驻马店463000

出　　处：《中国皮肤性病学杂志》2024年第12期1327-1332,共6页The Chinese Journal of Dermatovenereology

摘　　要：目的确诊1个遗传性血管性水肿患者家系,并对其C1抑制物(C1-INH)SERPING1基因进行分析。方法采用聚合酶链反应(PCR)和Sanger测序法对SERPING1基因的启动子、外显子及内含子区域进行检测,将检测结果与NCBI数据库标准序列进行比对。采用散射比浊法检测血清补体C4、C1-INH浓度,采用酶联免疫吸附试验(ELISA)法检测血清C1-INH功能。结果该家系共2例确诊遗传性血管性水肿,均为Ⅰ型。2例患者均携带同一致病变异,第6外显子均检测到1个移码杂合变异(c.933_934insGGAA),该变异导致编码第312位氨基酸由脯氨酸变为甘氨酸,并在位移后的第17位氨基酸提前出现终止密码子(p.P312Gfs*17)。该家系中12名正常对照均未检测到该变异。2例患者的血清C4、C1-INH浓度及功能水平均低于正常值下限,12名家系正常对照血清C4、C1-INH浓度及功能水平均在正常范围内。结论该遗传性血管性水肿家系SERPING1基因出现移码杂合变异(NM_000062)c.933_934insGGAA,该变异可能是导致此家系发病的遗传性病因。Objective To diagnose hereditary angioedema in a family of patients and analyze the locus of the C1 inhibitor(C1-INH)SERPING1 gene.Methods PCR and Sanger sequencing were applied to analyze promoter,exon and intron regions of the SERPING1 gene.The sequencing results were compared with the references from the NCBI database.Rate nephelometry assay was employed to detect serum complement C4 and C1-INH concentration,and ELISA assay was used to assess the levels of serum C1-INH function.Results Two members of the family were diagnosed with hereditary angioedema,both cases of typeⅠ.The 2 patients carried same pathogenic variant locus,and one frameshift heterozygous variation(c.933_934insGGAA)was detected in exon 6,which resulted in conversion of amino acid at position 312 from Pro to Gly,and caused a premature stop codon at the 17th amino acid following the frameshift(p.P312Gfs*17).The validation was not detected in the 12 unaffected family members.C4 and C1-INH concentrations and functional levels in the 2 patients were below the lower limits of normal range,while the results of 12 unaffected family members were within the normal ranges.Conclusion The frameshift heterozygous variation of the SERPING1 gene(NM_000062)c.933_934insGGAA is identified in this hereditary angioedema family,and the variation is likely responsible for disease onset genetically.

关 键 词：遗传性血管性水肿 C1抑制物 基因变异 SERPING1基因 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]