TSC2基因发生体细胞镶嵌突变导致结节性硬化症一例

A case of tuberous sclerosis induced by a somatic mosaic mutation in the TSC2 gene

目的报告1例TSC2基因发生体细胞镶嵌突变导致结节性硬化症患者的临床特点和基因突变情况。方法采集1例临床拟诊断结节性硬化症患者及其父母外周血提取基因组DNA，采用聚合酶链反应（PCR）及第二代测序法扩增TSC1和TSC2基因的全部外显子及其侧翼序列，并进行DNA测序分析，查找基因突变位点，以200例无关健康人DNA作为对照。提取患者皮损处皮肤组织DNA，利用PCR扩增TSC2基因目的片段并测序。结果患者临床出现面部血管纤维瘤、腰部色素减退斑、甲周纤维瘤及肾血管平滑肌脂肪瘤，符合结节性硬化症的诊断标准。患者TSC2基因存在c．5130_5131insT突变（p．V1711Cfs＊18），且瘤体DNA较外周血DNA携带更高频率突变。患者父母、无关正常对照及公开数据库均未发现该突变。结论TSC2基因发生体细胞镶嵌突变c．5130_5131insT是导致该患者较轻结节性硬化症表型的原因。

Objective To investigate clinical features and detect mutations in a case of tuberous sclerosis complex （TSC） caused by a somatic mosaic mutation in the TSC2 gene. Methods Peripheral blood samples were obtained from a patient with suspected TSC, his parents, and 200 unrelated healthy controls. Genomic DNA was extracted from these blood samples, polymerase chain reaction （PCR）and next- generation sequencing were performed to amplify all the exons and their flanking sequences of the TSC 1 and TSC2 genes followed by DNA sequencing, so as to identify mutations in the TSC 1 and TSC2 genes. DNA was also extracted from lesional skin tissues of the patient, and PCR was conducted to amplify the target fragment of the TSC2 gene followed by DNA sequencing. Results The patient clinically presented with facial angiofibroma, depigmented patches on the waist, periungual fibroma and angioleio-myolipoma of the kidney, which were consistent with the diagnosis of TSC. A mutation c.5130_5131insT（p.V1711Cfs＊ 18） was identified in the TSC2 gene in the patient. A higher frequency of the mutation was found in the DNA of the tumor tissue than in that of the peripheral blood. No such a mutation was found in his parents＇ DNA, unrelated healthy controls or any public database. Conclusion The somatic mosaic mutation c.5130_5131insT in the TSC2 gene is responsible for the phenotype of TSC in the patient.