目的　分析结节性硬化症的临床表现及基因变异情况。方法　回顾分析5个结节性硬化症家系成员的临床 资料及基因检测结果。结果　5个家系受累者多表现为不同程度的癫痫发作、色素脱失斑、智力低下。家系1先证者TSC1 基因存在c.2074C>T杂合无义突变，其父母该位点未见异常；家系2先证者TSC2基因存在c.2545+10C>T杂合变异，为 新发现的剪切变异，其父亲该位点为杂合子；家系3先证者TSC1基因存在c.2497C>T杂合无义变异，其母亲和姐姐该位 点均为杂合子；家系4先证者TSC2基因存在c.4375C>T杂合变异，为新发现的无义变异，其母亲、姐姐及哥哥该位点均为 杂合变异；家系5先证者未发现明确致病变异。结论　具有相同TSC1变异位点的结节性硬化症患儿的临床表现可各不相 同；发现新的TSC1致病变异。

　Objective　To evaluate the clinical manifestations and the frequency of gene mutations that associated with tuberous sclerosis from 5 families. Method　Peripheral blood samples from 5 families of the tuberous sclerosis family were collected, genomic DNA was extracted, then analying the clinical manifestations and mutations. Results　A heterozygous nonsense mutation of c.2074C>T in the TSC1 was detected in the proband of family 1, but the same mutation was not found from their parents.A c.2545+10C>T heterozygous mutation in the TSC2 gene, which was a new spilcing mutation, was found in the proband of family 2. The same mutation was found from her father. A c.2497C>T heterozygous mutation in the TSC1 gene was found in the proband of family 3, as well his mother and sister. A c.4375C>T heterozygous mutation in the TSC2 gene, as a newly discovered nonsense mutation, was found in the proband of family 4, and the mother, sister and brother were heterozygous mutations at this position. A mutation that clearly caused the disease was not found in the proband of family 5. The affected members of the five families performed multiple seizures of different severity, depigmentation macula, and intellectual disability. Conclusion　The pathogenicity of gene mutations in family 2 and 4 have not been reported, which is a new pathogenic mutation. The clinical manifestations of individuals with the same mutation site in the same family are of great different; the family 5 does not detect a pathogenic mutation, but clinical manifestations are typical, considering the possibility of mosaicism mutations.