一例TSC2基因新发突变导致结节性硬化症病例分析

One case of tuberous sclerosis caused by de novo mutated TSC2 gene

对1例散发性结节性硬化症(Tuberous sclerosis complex,TSC)患儿进行TSC1及TSC2基因检测,探讨其可能的发病机制。采集患儿及其父母外周血提取基因组DNA,通过二代测序(Next generation sequencing,NGS)技术对患儿TSCl和TSC2基因的全部外显子及其侧翼序列进行测序,对其父母行Sanger测序验证,采用多重连接探针扩增技术(multi-plexligation-dependent probe amplification,MLPA)检测患儿TSC1和TSC2基因大片段缺失,分析TSC的发病机制、临床特点和基因突变特征。本例患儿,男性,8个月龄,临床表现为癫痫发作及皮肤损害,查体:颜面部、左上、下肢皮肤可见4处牛奶咖啡斑,直径均大于5 mm。头颅磁共振成像示脑内多发异常信号及脑室内异常结节。NGS测序提示TSC2基因c.340G>T杂合突变,Sanger测序验证其父母均无上述变异,MLPA检测未发现患儿TSC1、TSC2基因存在大片段变异。TSC2基因c.340G>T点突变可能是该患儿结节性硬化症的致病突变。

To identify the pathogenic mutations of the TSC1 and TSC2 genes in a child with sporadic tuberous sclerosiscomplex. Peripheral blood samples were obtained from the child and his parents,all the exons and lateral sequences of TSC1 and TSC2 genes were sequenced by the next generation sequencing(NGS), and the sequence of the TSC2 gene of his parentswere confirmed by Sanger sequencing, multiplex ligation-dependent probe amplification(MLPA)of the TSCl and TSC2 geneswas performed as well. Combined with the literature, the pathogenesis, the clinical features and the mutation features of TSCwere reviewed. In this case, the patient, male, 8 months old, presented with seizures and skin lesions. Physical examination: 4spots of milk and coffee spots were visible on the face, upper left and lower limb skin, all of which were larger than 5 mm indiameter. Brain MRI showed multiple abnormal signals and abnormal nodules.Ophthalmic consultation: manifestations offundus sarcoidoid lesions.NGS sequencing suggested that TSC2 gene c.340G>T heterozygous mutation, and Sanger sequencingverified that none of his parents had the above mutation. MLPA test was normal. The c.340G>T point mutation of TSC2 genemay be a pathogenic mutation of tuberous sclerosis complex, which is a de novo mutation.