遗传性血管性水肿1家系C1抑制物基因突变分析

Mutation Analysis of C1 Inhibitor (C1INH) Gene in a Chinese Family with Hereditary Angioedema

目的对一个中国遗传性血管性水肿家系进行C1抑制物(C1INH)基因突变检测分析。方法采用聚合酶链反应(PCR)和直接测序法检测C1INH基因8个外显子及每个外显子与内含子的相邻序列,将检测结果与GenBank公布的C1INH基因正常序列进行比较。为除外基因多态性可能,在50名正常人群对照中对该突变进行分析。血清补体C4和C1INH浓度采用速率散射比浊法测定,血清C1INH功能水平通过酶联免疫吸附试验(ELISA)测定。结果 4例患者的第3外显子均检测到1个无义突变(c.400G>T),该突变导致编码第134位的谷氨酸变为终止密码子(p.E134X)。家系中4例正常对照和50例健康人群对照未检测到该突变。4例患者的血清C4浓度、C1INH浓度及功能水平均低于正常值下限。该家系中2例正常对照和2例健康人群对照血清C4浓度、C1INH浓度及功能水平均在正常范围内。结论在该家系中发现C1INH基因突变c.400G>T,该突变为此家系发病的分子基础。

Objective To detect and analyze the mutation of C1 inhibitor(C1INH)gene in a Chinese family with hereditary angioedema(HAE).Methods Polymerase chain reaction(PCR)and direct sequencing were applied to analyze all the 8 exons of the C1INH gene,as well as intron-exon boundaries.The sequencing results were compared with the standard C1INH gene sequences in GenBank.To exclude the polymorphism,50 healthy controls were included.Rate nephelometry assay was employed to detect serum complement C4 and C1INH concentration.ELISA assay was used to assess the levels of serum C1INH.Results One mutation(c.400G>T)was found in all 4 patients' exon 3,which resulted in Glu at position 134 replacement by a stop codon(p.E134X).The mutation was not detected in the 4 unaffected family members and 50 healthy controls.C4 and C1INH concentrations,C1INH levels in the 4 patients were below the lower limits of the normal range.The results of 2 unaffected family members and 2 healthy controls were within the normal ranges.Conclusion The mutation of the C1INH gene(c.400G>T)is identified in this family.Molecular diagnosis of HAE can be made by detecting the mutation.