Mutation Q301X In The PAX6 Gene Causes Congenital Aniridia In A Chinese Family

Aniridia is a severe intraocular congenital anomaly, and in general affects both eyes. The incidence is 1/96000-1/64000. Its pathological changes also involve the cornea, the crystalline lens, the retina and the optic nerve, and can associate with other diseases such as cataract, cloudiness of cornea, glaucoma, macular degeneration, and optic nerve maldevelopment. The patient usually displays lack of iris. The clinical symptoms of patients are photophobia and low vision, the cloudiness of cornea, cloudiness of crystalline lens and glaucoma which often cause patients to lose sight. Approximately 2/3 of the patients have the family history, and follow the autosomal dominant inheritance pattern. The remaining 1/3 of the patients are sporadic cases.We characterized a 3 generation family with autosomal dominant aniridia. We carried out detailed ophthalmic examinations for selected patients and normal family members. We carried out mutational analysis of the PAX6 gene in the family, and identified the Q301X (c.901C>T(Q301X)) mutation in the 11th exon. All patients in the family carry the mutation, but the normal family members do not carry the mutation. These results suggest that the Q301X mutation in the PAX6 gene is the causative factor in the Chinese family. This is the first time that the Q301X is identified in the Chinese population. Q301X is located in the domain rich in the proline, serine and threonine residues (PST) at the C-terminus. The mutation causes the PAX6 protein to terminate before the PST domain, generating a truncated protein without the PST domain and creating a non-fucntonal transcription factor. This study identifies a new mutation in the PAX6 gene in the Chinese population and expands the spectrum of PAX6 mutaitons causing the aniridia phenotype.