Peters综合征临床特征和基因突变的研究

Clinical and genetic research in Chinese families with Peters syndrome

目的:分析国人Peters综合征的临床特征,并确定致病基因突变,为该病的临床诊断和治疗及发病原因提供依据。方法:选取2012/2015年在常州市第二人民医院眼科就诊的10例先天性角膜混浊的患者,并收集详细的相关临床资料。征得患者及其家系成员的同意后抽血制备基因组DNA,用聚合酶链反应(PCR)对致病基因PITX2的编码区及其临接内含子进行扩增后,直接测序分析该基因。同时检测100位无亲缘关系的正常人外周血标本进行对照验证。结果:患者1例的临床特点包括先天性角膜中央部混浊白斑,伴有相应区域的角膜后部基质变薄和后弹力层缺损,且患者伴有全身系统如心脏和听力损害等改变,符合Peters综合征的临床诊断;该患者PITX2基因突变筛查结果发现了1种新突变,c.788G>A,导致该基因的功能异常,而家属中表型正常者及无亲缘关系的正常对照者均未发现该基因突变。结论:先天性角膜混浊患者10例中检测到1个新PITX2基因突变,符合Peters综合征的临床诊断,这是中国首次报道Peters综合征的PITX2基因突变,结果丰富了PITX2基因突变频谱,并进一步明确了Peters综合征的临床特点,为该病的临床诊断和治疗及发病原因提供了依据。

AIM：To research the clinical characteristics and identify the disease- causing gene mutation in Chinese patients with Peters syndrome. All these cases will be useful foundations for clinical diagnosis,medical therapy and pathogenesis. METHODS： Ten congenital corneal opacities affected patients were enrolled fromour pediatric and genetic eye clinic. M edical and ophthalmic histories were obtained.Genomic DNA was prepared fromvenous leukocytes after informed consent conforming was obtained fromeach participant. The coding regions and the flanking exon- intron junctions of this gene were amplified by polymerase- chain reaction（ PCR） and subsequently analyzed by direct sequencing. Variations detected were further evaluated in 100 normal controls by direct sequencing. RESULTS： One affected individual characterized by systemic changes such as congenital heart anomalies and hearing loss showed the consistent phenotypes with Peters syndrome. Sequence analysis of the PITX2 gene revealed one novel mutation, c. 788 G〉 A. Nucleotide sequence analysis showed that this mutation led to the functional abnormal of this gene,however,no mutationwas observed in any unaffected member or 100 normal unrelated individuals. CONCLUSION： A novel mutation in the PITX2 gene have been identified,this is the first report on a mutation in a Chinese Peters syndrome and the result expand the mutation spectrumof PITX2,further clarify the clinical features of the disease. All these will be useful foundations for clinical diagnosis,medical therapy and pathogenesis.