论文部分内容阅读
目的探索有效的突变检测技术,系统分析家族性腺瘤样息肉病(familialadenomatouspolyposis,FAP)相关基因结肠腺瘤病(adenomatouspolyposiscoli,APC)基因的胚系突变,及其与疾病表型的关系。方法从22例临床确诊的FAP患者,外周静脉血中提取基因组DNA。变性高效液相色谱、蛋白截短检测、测序技术结合应用进行全基因分析。根据患者临床资料,进行基因型表型分析。结果22例FAP患者中13例检出APC基因胚系突变,均为无义或移码突变。基因型-表型关系的初步分析表明,在基因5′端或3′端发生突变的患者临床症状较轻,在基因中段发生突变的患者临床症状典型或严重。结论本研究中所采用的技术体系可敏感、高效地检出APC基因突变,APC基因的突变型与FAP患者的临床表型存在关联,所采用的技术体系适用于FAP症状出现前的基因诊断。
Objective To explore an effective mutation detection technique to systematically analyze the germline mutation of familial adenomatous polyposis coli (APC) gene and its relationship with disease phenotype. Methods Genomic DNA was extracted from peripheral venous blood of 22 patients with FAP clinically diagnosed. Denaturing high performance liquid chromatography, protein truncation detection, sequencing technology combined with the application of whole genome analysis. According to the clinical data of patients, genotype phenotype analysis. Results APC gene germline mutation was detected in 13 out of 22 FAP patients, all of which were nonsense or frameshift mutations. Preliminary analysis of genotype-phenotype relationships showed that patients with mutations in the 5 ’or 3’ end of the gene had mild clinical symptoms and those with mutations in the middle of the gene were either typical or severe. Conclusion The technique system adopted in this study can detect APC gene mutation sensitively and efficiently. The APC gene mutation phenotype is associated with the clinical phenotype of FAP patients. The technique system used is suitable for gene diagnosis before FAP symptom.