Phenotypic variations in patients with a 1630 A>T point mutation in the PAX6 gene.

Background: The extreme clinical case-to-case variability of aniridia, even within families, can cause difficulties in making the correct diagnosis, prognosis and treatment plan. We describe seven patients from two families demonstrating variable expression of this syndrome, all with the same single point mutation within the PAX6 gene.

Methods: Case presentations. The authors review the clinical ophthalmic findings of the aniridia-keratopathy syndrome from two families, one involving four generations, the other with two generations. Polymerase chain reaction amplification of all 14 exons of the PAX6 gene was performed for five patients.

Results: The iris findings varied from classic total absence to nearly normal iris appearance. Corneal changes were minimal in the younger patients but vision-impairing in the older. None of the patients had glaucoma. The five patients who underwent DNA analysis shared the same PAX6 point mutation defect (1630A>T).

Interpretation: Bilateral corneal changes progressing from mild opacification at the limbus to vascularized central keratopathy, especially in the presence of nystagmus, are highly suggestive of a PAX6 mutation. Such patients may theoretically benefit from early limbal stem cell replacement therapy.