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

Abstract

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.

Keywords

• peters'anomaly
• axenfeld-rieger syndrome
• pitx2 gene
• pax6 gene
• mutation