先天性睑裂狭窄综合征患者FOXL2基因突变研究

发布时间：2018-05-06 08:50

本文选题：BPES + FOXL2基因　；参考：《浙江大学》2010年硕士论文

【摘要】： 目的：对8例先天性睑裂狭窄综合征(BPES)患者(两个家系中4例,散发患者4例)FOXL2基因序列进行检测,以明确突变位点及突变类型,预测突变引起的基因表达变化,提高疾病的诊断准确率并为基因治疗的实施打下坚实的基础。方法：采集BPES患者及家属外周静脉血5ml,提取血基因组DNA,共设计3对PCR引物,应用聚合酶链反应(PCR)和DNA测序技术对FOXL2基因编码区域进行突变检测。结果：两个家系中4例患者均检测到c.672_701dup30重复突变,散发患者中除一例未检测到FOXL2基因突变外,其他三例患者分别检测到c.655CT无义突变,c.370AG错义突变和c.858_874dup17重复突变,家系中未患病者及散发病例的直系亲属中均未检测到相应突变。结论：首次在散发BPES患者中发现FOXL2基因c.370 AG错义突变和c.858_874dup17重复突变,扩展了FOXL2基因突变谱,在两个家系中均发现c.672_701dup30重复突变,再次证明这一位点为BPES患者FOXL2基因突变热点。未检测到FOXL2基因突变的BPES患者可能与染色体畸变有关,有必要进行染色体分析。
[Abstract]:Objective: The sequence of FOXL2 gene was detected in 8 patients with congenital blepharostenosis syndrome (4 out of 2 families and 4 sporadic patients) in order to identify the mutation site and mutation type and predict the gene expression changes caused by mutation. To improve the diagnostic accuracy of disease and lay a solid foundation for the implementation of gene therapy. Methods: Genomic DNA was extracted from peripheral venous blood of BPES patients and their relatives. Three pairs of PCR primers were designed. The mutation of FOXL2 gene coding region was detected by polymerase chain reaction (PCR) and DNA sequencing. Results: C.672_701dup30 repeat mutations were detected in 4 patients in two families, except for one patient without FOXL2 gene mutation in sporadic patients, the missense mutation and c.858_874dup17 repeat mutation in c.655CT nonsense mutation / c. 370 AG and c.858_874dup17 repeat mutation were detected in the other three patients, respectively. No corresponding mutations were detected in the unaffected families and in the immediate relatives of sporadic cases. Conclusion: For the first time, FOXL2 gene c. 370 AG missense mutation and c.858_874dup17 repeat mutation were found in sporadic BPES patients, which extended the FOXL2 gene mutation spectrum, and c.672_701dup30 repeat mutation was found in both families. It was proved that this point was the hot spot of FOXL2 gene mutation in BPES patients. The BPES patients without FOXL2 gene mutation may be related to chromosome aberration, so it is necessary to carry out chromosome analysis.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R777

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