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目的:分析一个中国人结节性硬化症家系的临床特征，并探讨其发病的分子机制。方法:收集先证者及其家系成员的临床资料，采用全外显子组测序技术对先证者外周血DNA的n TSC1和n TSC2基因变异进行鉴定。经生物信息学分析后，对发现的潜在致病变异采用Sanger测序法对父母进行验证。n 结果:先证者及其母亲均携带n TSC2基因新的c.4183C>T(p.Q1395X)杂合变异，生物信息学分析提示该变异为潜在的致病变异。先证者母亲同样诊断为结节性硬化症，但症状轻于患者。另外4名未患病的家系成员未发现上述突变。n 结论:TSC2基因新的c.4183C>T(p.Q1395X)杂合变异可能是该家系的致病原因。上述发现扩大了n TSC2基因的突变谱。先证者症状重于其母亲考虑与表型异质性有关。n “,”Objective:To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis.Methods:Clinical data of the proband and members of his pedigree were collected. Whole exome sequencing was carried out to detect variants of the n TSC1 and n TSC2 genes. Candidate variants was verifed by Sanger sequencing and bioinformatic analysis.n Results:The proband and his mother, who also had mild features of tuberous sclerosis, were found to harbor a novel heterozygous c. 4183C>T (p.Q1395X) variant of then TSC2 gene, which was absent in the 4 healthy relatives. Bioinformatic analysis suggested the variant to be likely pathogenic.n Conclusion:The heterozygous c. 4183C>T (p.Q1395X) variant of then TSC2 gene probably underlay the disease in this pedigree. Above finding has expanded the spectrum of n TSC2 gene variants. The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.n