关键词: 结节性硬化症；　TSC1基因；　TSC2基因；　新突变；　临床表现

Abstract: 　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.

Key words: 　tuberous sclerosis;　TSC1 gene;　TSC2 gene;　new mutation;　clinical manifestation