【摘要】 目的结节性硬化症（TSC）是一种累及多系统的常染色体显性遗传病,以全身多种组织器官出现错构瘤样增生为主要特征,其致病基因为TSC1和TSC2基因,本研究旨在对一中国汉族结节性硬化症家系进行基因突变分析,以明确临床诊断并指导遗传咨询。方法设计PCR引物,扩增TSC1和TSC2外显子及外显子-内含子交界区并进行Sanger测序和片段克隆测序分析,确定突变位点并探讨突变致病的可能机制。结果 TSC1基因测序分析发现先证者第15外显子存在两个杂合突变,c.1556C>T和c.1888₁891del AAAG。克隆测序结果显示,先证者的两个突变均来自于同一个等位基因。第一个突变可能影响TSC1与粘着斑激酶家族作用蛋白FIP200的结合,第二个突变形成了提前的终止密码,推测可能形成截短的蛋白分子,或者通过无义介导的m RNA降解机制被降解而致病。结论TSC1基因c.1556C>T和c.1888₁891del AAAG为结节性硬化症家系致病突变,对患者明确诊断及遗传咨询有重要意义。更多还原

【Abstract】 Objective uberous sclerosis complex（TSC）is an autosomal dominant genetic disease involving multiple systems,characterized by hamartoma hyperplasia in a variety of tissues and organs.TSC is caused by the mutation in TSC1 or TSC2.This study aimed to detect gene mutations in a Chinese Han TSC family,establish definitive diagnosis and provide genetic counseling.Methods The PCR primers covering all the TSC1 and TSC2 exons and exon-intron boundaries were designed,then Sanger sequencing and cloning sequencing analysis were performed to explore pathogenic mechanism of the mutation.Results We found two heterozygous mutations in exon 15 of TSC1,c.1556C>T and c.1888₁891del AAAG;two mutations are from the same allele,the first mutation may affect interaction between TSC1 and focal adhesion kinase[FAK] family interacting protein of 200 k D（FIP200）,the second mutation resulted in a premature stop codon that may form a truncated TSC1 m RNA molecule,or degraded by nonsense mediated m RNA degradation.Conclusion TTSC1 gene c.1556C> T and c.1888₁891del AAAG are pathogenic mutations for the TSC family,which is of great significance to patient’s diagnosis and genetic counseling.更多还原