Purpose: To identify novel mutation in the PAX6 (paired box gene 6) gene and characterize new clinical features of severe ocular malformation in a Chinese patient with Peters' anomaly.
Methods: A 10-month-old male infant, who presented with corneal opacity and nystagmus, was referred to our pediatric clinic and underwent a complete general physical and ophthalmological examination, including anterior segment and retinal evaluation with slit-lamp microscopy, an A/B ultrasonic scan, and electroretinography (ERG). Genomic DNA was prepared from venous leukocytes. The coding regions and the adjacent intronic sequence of PAX6 were amplified by a polymerase chain reaction, and subsequently analyzed by direct sequencing. The variation detected was further evaluated in 100 controls using heteroduplex- single strand conformational polymorphism (SSCP) analysis.
Results: The patient had bilateral Peters' anomaly showing congenital nystagmus, corneal leukoma with anterior synechia, anterior polar cataract, and his pupils could not be dilated because of posterior synechia. Electroretinography (ERG) demonstrated retina hypogenesis and an A/B ultrasonic scan showed microphthalmus. A novel mutation: C.51C>A (P. N17K) was identified in PAX6 while this mutation was absent in 100 normal controls. This mutation, which affects highly conserved amino acid, has not been previously reported.
Conclusions: PAX6 mutations cause ocular malformations that vary considerably in pattern and severity. In this study, we identified one novel mutation in PAX6 in a patient with severe ocular clinical features of Peters' anomaly. This finding expands the mutation spectrum in PAX6 and enriches our knowledge of genotype-phenotype relations due to PAX6 mutations.