PAX6 aniridia and interhemispheric brain anomalies.

Area of Science:

• Genetics and Ophthalmology
• Human Molecular Genetics
• Neurodevelopmental Disorders

Background:

• Aniridia is a rare genetic disorder characterized by the absence of iris tissue.
• Mutations in the Paired Box gene 6 (PAX6) are a primary cause of aniridia.
• The spectrum of clinical manifestations and associated anomalies requires further investigation.

Purpose of the Study:

• To conduct a clinical and genetic study of patients with autosomal dominant aniridia.
• To identify mutations in the PAX6 gene and correlate them with clinical phenotypes.
• To investigate the association between aniridia and potential cerebral anomalies.

Main Methods:

• Ophthalmologic, general, and neurological examinations were performed on ten patients from three Egyptian families.
• Cerebral magnetic resonance imaging (MRI) was conducted on index patients.
• Genomic DNA was analyzed using direct sequencing of all PAX6 exons and intron-exon junctions.

Main Results:

• All patients exhibited absence of iris tissue, corneal pannus, and foveal hypoplasia, leading to reduced visual acuity.
• Two novel PAX6 mutations (c.170-174delTGGGC [p.L57fs17] and c.475delC [p.R159fs47]) and one known mutation (c.718C>T [p.R240X]) were identified.
• Cerebral MRI revealed absence of the pineal gland in all index patients, with specific brain anomalies correlating with different PAX6 mutations.

Conclusions:

• Two novel PAX6 mutations associated with severe aniridia were identified.
• Aniridia is linked to specific brain anomalies, including pineal gland absence and interhemispheric abnormalities, even with normal neurological examinations.
• The study underscores the genetic heterogeneity of PAX6 mutations and the varied spectrum of associated brain anomalies.