结节性硬化的临床特点和基因突变分析(附2例报告)

Clinical and genetic characterizations of cerebral tuberous sclerosis(report of 2 cases)

目的探讨结节性硬化(TSC)的基因突变,临床以及影像学特征。方法回顾性分析2例临床确诊的TSC患者的临床表现,用代表性图例展示室管膜下结节,皮质神经管以及骨质多发结节等影像学特征。并通过文献检索总结分析中国结节性硬化1型(TSC1)患者的临床和基因特征。结果两例临床确诊的TSC的患者,1例为TSC1新位点突变即c.1998-2A>G,此位点突变为剪切突变。文献检索具有TSC1详细基因报道的中国人群62例(含本篇报道1例),其中散发病例占51.61%,家族性病例占48.39%。突变类型主要包括:缺失突变(32.26%),无义突变(22.58%),插入突变(12.90%),剪切突变为(6.45%),错义突变(25.80%),单核苷酸多态性(4.84%),其中有3例患者出现两种突变形式。临床主要表现为低色素结节(68.97%),面部血管瘤(56.90%),室管膜下结节(55.17%),癫痫(53.45%)等。结论 TSC属于临床少见疾病,且并不一定具有家族史。临床上以癫痫起病,面部低色素结节,影像学上具有皮质神经管以及室管膜下结节的特点,出现类似病例要考虑基因检测,有助于临床诊断。

Objective To explore the genetic mutations, clinical and imaging characteristics of tuberous sclerosis(TSC). Methods Clinical and imaging characterizations of two TSC patients were analyzed retrospectively. Representative imaging features including subependymal nodules, cortical tubers and multiple bone nodules were presented. The clinical and genetic characteristics of patients with tuberous sclerosis type 1(TSC1) in Chinese population were analyzed by literature review.Results Of the two TSC patients, one novel mutation site of TSC1 was found. That is c. 1998-2 A>G, a shear mutation. By literature review: 62 cases(including 1 case reported in this paper) were summarized with detailed TSC1 gene reports, among which, sporadic cases accounted for 51.61% and familial cases accounted for 48.39%. The mutation types mainly included deletion mutation(32.26%), nonsense mutation(22.58%), insertion mutation(12.90%), shear mutation(6.45%), missense mutation(25.80%), and single nucleotide polymorphism(4.84%), among which 3 patients showed two mutation types. The main clinical manifestations were hypopigmentation nodules(68.97%), facial hemangioma(56.90%), subependymal nodules(55.17%), epilepsy(53.45%), etc.Conclusions TSC is a rare clinical disease and family history is sometimes absent. Clinically, if patients presented with epileptic onset, facial hypopigmentation nodules, and imaging features of cortical tubers and subependymal nodules, genetic testing should be considered to help accurate clinical diagnosis.