PAX 6 is normal in most cases of Peters' anomaly.

Abstract Mutations in the PAX 6 gene are known to cause many cases of inherited and sporadic aniridia. Although embryologically similar to aniridia, the cause of Peters' anomaly has received far less attention. Two reports have been published demonstrating mutations in the PAX 6 gene in Peters' anomaly. We have analysed the PAX 6 gene in 15 individuals with Peters' anomaly (7 familial, 8 sporadic). This is the largest cohort of Peters' anomaly described. The PAX 6 gene was screened using a combination of single-strand conformational polymorphism gel electrophoresis and direct sequencing. No mutations were found in the coding region of the PAX 6 gene. We feel that Peters' anomaly is a heterogeneous condition and that for the majority of cases PAX 6 is not the 'Peters' anomaly gene'. Key words PAX 6, Peters' anomaly Introduction Peters' anomaly is a congenital abnormality affecting the anterior segment of the eye. Both eyes are usually affected. The striking feature is corneal opacification, which may be central or peripheral, with underlying defects in the posterior stroma, Descemet's membrane and endothelium. There are frequently iris synechiae to the periphery of the opacity and less commonly keratolenticular strands. It is generally accepted that 50% of affected individuals will develop glaucoma in childhood. Embryologically Peters' anomaly is thought to arise as a result of defective neural crest cell migration in the sixth to eighth weeks of fetal development during which the anterior segment of the eye forms.! The PAX 6 gene has been implicated in the control of neural crest cell migration, with mutations giving rise to characteristic ocular phenotypes. Heterozygous nonsense mutations in PAX 6 are responsible for many cases of sporadic and familial aniridia, as a result of haploinsufficiency.2 It has been proposed that missense mutations, where the protein is translated but with one amino acid A.J. CHURCHILL, A.P. BOOTH, R. ANWAR, A.F. MARKHAM substitution, may give rise to a variety of eye conditions such as Peters' anomaly, atypical aniridia or foveal hypoplasia.3 There have, however, only been two reports in the literature linking Peters' anomaly and PAX 6.4." The purpose of this study was to determine whether any PAX 6 mutations could be found amongst 15 individuals with Peters' anomaly. Patients and methods Ethics approval was obtained from the Leeds (East) Medical Research (Ethics) Committee. Affected individuals and family members were contacted by letter inviting their participation in this study. All those who accepted were seen in their local eye department and, after a full discussion about the research, underwent an eye examination using a slit-lamp biomicroscope, in addition to gonioscopy, applanation tonometry and fundoscopy where appropriate. A blood sample was collected into a tube containing EDT A, and anterior segment photographs were taken where possible. When the individual was too young for a detailed exmination in the clinic this was performed under anaesthesia when it was next indicated for clinical reasons. A total 15 individuals were examined; 7 had probable familial Peters' anomaly (from