Peters异常PITX2及PAX6基因型表型分析

目的：分析中国人Peters异常(PA)患者的临床特征，研究Peters异常患者PITX2及PAX6基因变异情况。

方法：选取2016/2019年在常州市第二人民医院及第三人民医院眼科就诊的15例Peters异常患者，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及PAX6的编码区及其临接内含子进行扩增后，直接测序筛查中国人群Peters异常患者PITX2及PAX6基因变异，异源双链-单链构象多态性分析(HA-SSCP)的方法对突变患者及其家系成员及80例正常对照进行验证； 分析比较国内已报道的Peters异常患者PITX2及PAX6基因突变并研究其相关表型。

结果：Peters异常患者15例PITX2基因突变筛查结果发现了1种新PITX2的突变c.296delG(P.R99fsx56)，导致该基因的功能异常，分析突变患者临床特征，该患者右眼诊断为Axenfeld-Rieger综合征(ARS)，左眼诊断为Peters异常。而家系成员中该患者父母及无亲缘关系的正常对照者均未发现相同突变，故此突变为新生突变。PAX6基因突变筛查未能发现突变。

结论：PA患者15例中检测到1个新PITX2基因突变，丰富了PITX2基因突变频谱，进一步明确了PA合并ARS眼病的临床特点，为该种少见眼病的临床诊断和发病原因提供了依据。

Genotype-phenotype analysis in Peters' anomaly patients with PITX2 and PAX6 genes

AIM: To analyze the clinical characteristics of patients with Peters'' anomaly(PA)in Chinese, and to study the variation of PITX2 and PAX6 genes in patients with PA, so as to provide basis for clinical diagnosis and pathogenesis of this rare ophthalmopathy.

METHODS: Fifteen patients with PA were selected from 2016 to 2019 in Changzhou No. 2 People''s Hospital and Changzhou No. 3 People''s Hospital, and the detailed clinical data were collected. Genomic DNA was prepared from venous leukocytes after obtaining the consent of the patients and their family members. The coding regions and the flanking exon-intron junctions of the PITX2 and PAX6 genes were amplified by polymerase-chain reaction(PCR)and subsequently analyzed by direct sequencing. Variations detected were further evaluated in any unaffected member and 80 normal controls by HA-SSCP. Analyzing and comparing the mutation of PITX2 and PAX6 genes and the related phenotypes in Chinese patients with PA.

RESULTS:Sequence analysis of the PITX2 gene revealed one novel mutation c.296delG(P.R99fsx56)in fifteen patients with PA. Nucleotide sequence analysis showed that this mutation led to the functional abnormal of this gene. The clinical characteristics of the mutant patient were analyzed, the right eye of the patient was diagnosed as Axenfeld-Rieger syndrome(ARS), and the left eye was diagnosed as Peters''anomaly. However, the mutation was not found in the family members of the patient''s parents and unrelated normal controls, and therefore it was a de novo mutation. No mutation was found in PAX6 gene mutation screening.

CONCLUSION: A novel PITX2 gene mutation was detected in 15 patients with PA, which was the first report of PITX2 gene mutation in a patient with Peters''anomaly complicated with ARS in China. The results enrich the mutation spectrum of PITX2 gene and further clarify the clinical characteristics of PA complicated with ARS. All these will be useful foundations for clinical diagnosis and pathogenesis. Furthermore, it enriches our knowledge of genotype-phenotype relationship of PA. In addition, our results may provide basis for the functional and genomic study of the pathogenesis of the disease in the future.