结节性硬化症TSC2基因5238-5255 del 18 bp及2713 C>T基因突变分析

目的检测并分析2例中国汉族结节性硬化症(tuberous sclerosis complex,TSC)患者TSC2基因突变特点。方法采用直接测序法对31个家系的34例TSC患者及其父母33名进行TSC1基因和TSC2基因全长编码外显子基因检测。测序后发现第25家系先证者为TSC2基因外显子40的框内移码突变5238-5255 del 18 bp,第11家系先证者为TSC2基因外显子23错义突变Arg905Trp。进一步采用变性凝胶电泳及内切酶技术在患者与120名正常对照中检测这两种突变。结果第25家系先证者外显子40出现5238-5255d el CATCAAGCGGCTCCGCCA突变,导致6个氨基酸缺失的框内移码突变(1746-1751del His-Ile-Lys-Arg-Leu-Gly),第11家系先证者外显子23出现2713 C>T(Arg905Trp)错义突变,2713位碱基由胞嘧啶(C)改变为胸腺嘧啶(T),导致第905位氨基酸精氨酸被色氨酸替代。120名正常对照未检测到这两种突变。结论TSC2基因5238-5255 del 18 bp及2713 C>T突变为两种致病性突变。

Analysis of 5238 -5255 del 18 bp and 2713 C>T mutaitons in TSC2 gene in two Chinese patients with tuberous sclerosis complex

Objective To study the characteristic of TSC2 gene mutations in two han Chinese patients with tuberous sclerosis complex.Methods Thirty four patients with clinically confirmed TSC and 33 parents of the patients coming from 31 TSC families were included.Mutation analysis was performed by direct sequencing of all coding exons of the TSC1 and TSC2 genes.A in-frame shift mutation 5238-5255 del 18 bp in exon 40 of TSC2 gene and a missense variant 2713 C>T in exon23 of TSC2 gene were found in the probands of families 25 and 11,respeltively.The in-frame shift mutation was furtherly confirmed by denaturing gel electrophoresis in the proband of family 25 and 120 unrelated healthy control subjects,and the missense mutation was confirmed by restriction enzyme AccIII in the proband of family 11,the patients' father and 120 control subjects.Results The in-frame shift mutation 5238-5255 del CATCAAGCGGCTCCGCCA in exon 40 of TSC2 gene in the proband of family 25 resulted in a truncated protein 1746-1751del His-Ile-Lys-Arg-Leu-Gly.The missense mutation 2713 C>T in exon 23 of TSC2 gene in the proband of family 11 resulted in arginine 905 to tryptophane substitution.Conclusions These two reported mutations 5238-5255 del 18 bp and 2713 C>T are disease-causing mutations in TSC2 gene.