目的:探讨1例结节性硬化症(tuberous sclerosis complex, TSC)患者可能的遗传学病因。方法:应用高通量测序技术、多重连接探针扩增技术和Sanger测序技术对1例疑似结节性硬化症患者行基因变异分析，并在家系其他成员及100名正常对照中进行验证；通过反转录-PCR及Sanger测序技术确定该变异可能导致的mRNA转录变化。结果:测序结果显示该家系中先证者发生了n TSC2基因的c.2355+1G>C杂合变异，cDNA的序列分析表明该变异导致n TSC2基因在第21外显子3′端插入62个碱基序列，这种剪切位点变化导致蛋白翻译提前终止，预测产生截短蛋白。n 结论:TSC2基因c.2355+1G>C变异可能是该患者的致病原因。本研究结果不仅进一步丰富了n TSC2基因的变异谱，同时为产前诊断和胚胎植入前遗传学检测的开展提供了理论基础。n “,”Objective:To explore the genetic basis for a patient with tuberous sclerosis complex.Methods:Genomic DNA was extracted from peripheral blood samples from members of his family and 100 unrelated healthy controls. The proband was subjected to next-generation sequencing, and candidate variant was confirmed by multiple ligation-dependent probe amplification (MLPA)and Sanger sequencing. Reverse transcription-PCR (RT-PCR) was carried out to determine the relative mRNA expression in the proband.Results:The patient was found to harbor a c. 2355+ 1G>C splicing variant of then TSC2 gene. Sequencing of cDNA confirmed that 62 bases have been inserted into the 3′ end of exon 21, which has caused a frameshift producing a truncated protein.n Conclusion:The novel splicing variant c. 2355+ 1G>C of then TSC2 gene probably underlay the TSC in the proband. Above finding has expanded the variant spectrum of n TSC2 and provided a basis for preimplantation genetic testing and/or prenatal diagnosis.n