PAX6 mutations identified in 4 of 35 families with microcornea.

PURPOSE: Mutations in paired box gene 6 (PAX6) are the major cause of aniridia that may associate with several other developmental anomalies of the eye, including microcornea in rare cases. However, systemic evaluation of PAX6 in patients with microcornea as the major sign has not been reported. This study aims to detect PAX6 mutations in patients with microcornea.

METHODS

Genomic DNA of probands was prepared from 35 families with microcornea. The coding regions of PAX6 were screened by Sanger sequencing and novel variations were further evaluated in 192 normal individuals. Bioinformatics analysis was used to evaluate the structural consequences related to the pathology of the mutations.

RESULTS

The average corneal horizontal diameter of the 35 probands is 8.03 ± 1.27 mm (the median value is 8 mm). Among them, eight patients presented with normal iris, one had aniridia, and different severities of iris hypoplasia were detected in the rest. In four probands, three heterozygous variations in PAX6 were identified: a novel c.83_85delAGA (p.Lys28del) in two families; a novel c.337G>C (p.Ala113Pro) in one family; and a known c.399_399+5del6 in one family. None of the variations were detected in 192 normal individuals. Two of the four probands had partial iris while the other two presented with full iris.

CONCLUSIONS

We identified two novel and a known mutation of PAX6 in four probands with microcornea, accounting for 11.4% of microcorneas in this cohort. The findings not only expand the spectrum of PAX6 mutations, but also suggest that PAX6 mutations may be a common cause of microcornea.