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研究目的:对1个Axenfeld-Rieger综合征家系的临床特点及基因突变进行研究,探索Axenfeld-Rieger综合征发病的遗传机制。研究方法:对该Axenfeld-Rieger综合征家系进行全面临床检查,对家系成员应用聚合酶链反应(PCR)扩增PITX2基因和FOXC1基因的所有外显子及相邻内含子,对其产物进行直接测序并对PITX2基因第5个外显子进行克隆测序。选取100名健康者作为对照组,应用PCR扩增PITX2基因第5个外显子并进行直接测序。应用SWISS-MODEL软件对野生型和突变型的PITX2蛋白同源域进行建模分析。重要结论:该Axenfeld-Rieger综合征家系的眼部表型多样,但是各患者的全身系统异常却呈现一致性(见图2;表1)。基因测序结果显示先证者及其他患者均具有PITX2基因杂合突变c.198_201delins TTTCT(p.M66Ifs*133)。尽管PITX2基因突变引起Axenfeld-Rieger综合征已经被广泛证实,但是PITX2基因缺失/插入移码突变引起的Axenfeld-Rieger综合征仅被报道过一次,我们的研究首次在中国人群中揭示了这种罕见的突变方式。
Objective: To investigate the clinical features and gene mutations of a family of Axenfeld-Rieger syndrome and explore the genetic mechanism of Axenfeld-Rieger syndrome. Methods: A comprehensive clinical study of the Axenfeld-Rieger syndrome pedigree was conducted. Members of the family were subjected to polymerase chain reaction (PCR) to amplify all exons and adjacent introns of the PITX2 gene and FOXC1 gene, and their products were subjected to Direct sequencing and sequencing of the fifth exon of PITX2 gene were performed. 100 healthy individuals were selected as the control group. The fifth exon of PITX2 gene was amplified by PCR and sequenced directly. The wild-type and mutant PITX2 protein homology domains were modeled using SWISS-MODEL software. Important Conclusions: The Axenfeld-Rieger syndrome pedigrees have multiple ocular phenotypes, but systemic abnormalities are consistent across patients (Figure 2; Table 1). Gene sequencing showed proband and other patients have PITX2 gene heterozygous mutation c.198_201delins TTTCT (p.M66Ifs * 133). Although Axenfeld-Rieger syndrome has been widely confirmed by mutations in the PITX2 gene, Axenfeld-Rieger syndrome caused by a deletion / insertion frameshift in the PITX2 gene has been reported only once. Our study, for the first time in China, revealed this rare The way of mutation.