结节性硬化症家系的临床特点和基因突变分析

Analysis of clinical features and genetic mutation of tuberous sclerosis families

目的探讨结节性硬化症(TSC)家系的临床特点和基因突变情况,为TSC临床诊断提供依据。方法回顾性分析2014年1月至2019年12月北京协和医院确诊的10个TSC家系先证者及其成员的病例资料,进行详细的病史采集和查体。共26例患者,男12例,女14例,男女比例1∶1.17。年龄7~65岁。皮肤病变方面,面部血管纤维瘤24例,色素脱失斑20例,指(趾)甲纤维瘤16例,鲨革斑9例。12例患肾血管平滑肌脂肪瘤(RAML),4例头颅CT检查发现室管膜下结节(SEN),1例患肺淋巴管肌瘤病(LAM)。4例有癫痫发作病史。提取患者外周血进行DNA高通量测序。结果共23例TSC患者进行基因检测,6个家系共14例为TSC2基因突变,分别为移码突变5例、杂合缺失5例、无义突变4例;2个家系共4例为TSC1基因无义突变;2个家系未见突变。结论TSC家系患者主要存在皮肤表现和肾脏病变。基因突变方面以TSC1/2突变为主,其中又以TSC2突变主。无基因突变家系的患者主要表现为面部血管纤维瘤和/或色素脱失斑。

Objective Analysis of the clinical characteristics and genetic mutations of ten tuberous sclerosis complex(TSC)families to provide support for clinical diagnosis of TSC.Methods Retrospective analysis of ten TSC family probands and their members were performed with detailed medical history collection and physical examination.The study consisted of 26 patients in 10 TSC families,including 12 males and 14 females,with male to female ratio of 1∶1.17,and aged 7-65 years.In terms of skin lesions,there were 24 cases of facial angiofibromas,20 cases of hypomelanotic macules,16 cases of ungual fibromas,and 9 cases of shagreen patch.There were 12 cases of renal angiomyolipoma,4 cases of subependymal nodules based on craniocerebral CT,and 1 case of lymphangioleiomyomatosis.Four cases had a history of seizures.Peripheral blood was extracted for next generation DNA sequencing.Results A total of 23 TSC patients were genetically tested,and a total of 14 patients in 6 families were TSC2 mutations(5 frameshift mutations,5 heterozygous deletions,and 4 nonsense mutations),a total of 4 patients in 2 families were TSC1 nonsense mutations,and no mutations were seen in the 2 families.Conclusions A total of 10 TSC families were summarized,and the patients mainly had skin manifestations and kidney lesions.There were 18/23 patients having TSC1/2 mutations,of which TSC2 mutations accounting for 14/18.In the two non-mutant families,patients mainly had facial angiofibroma and/or hypomelanotic macules.