PAX6 aniridia and interhemispheric brain anomalies

[摘要] Purpose: To report the clinical andgenetic study of patients with autosomal dominant aniridia. Methods: We studied ten patients withaniridia from three families of Egyptian origin. All patients underwentfull ophthalmologic, general and neurological examination, and blooddrawing. Cerebral magnetic resonance imaging was performed in the indexcase of each family. Genomic DNA was prepared from venous leukocytes,and direct sequencing of all the exons and intron–exon junctions of thePaired Box gene 6 (PAX6) was performed after PCR amplification.Phenotype description, including ophthalmic and cerebral anomalies,mutation detection in PAX6 and phenotype-genotype correlationwas acquired. Results: Common features observed in thethree families included absence of iris tissue, corneal pannus withdifferent degrees of severity, and foveal hypoplasia with severelyreduced visual acuity. In Families 2 and 3, additional findings, suchas lens dislocation, lens opacities or polar cataract, and glaucoma,were observed. We identified two novel (c.170-174delTGGGC [p.L57fs17]and c.475delC [p.R159fs47]) and one known (c.718C>T [p.R240X]) PAX6mutations in the affected members of the three families. Systemic andneurological examination was normal in all ten affected patients.Cerebral magnetic resonance imaging showed absence of the pineal glandin all three index patients. Severe hypoplasia of the brain anteriorcommissure was associated with the p.L57fs17 mutation, absence of theposterior commissure with p.R159fs47, and optic chiasma atrophy andalmost complete agenesis of the corpus callosum with p.R240X. Conclusions: We identified two novel PAX6mutations in families with severe aniridia. In addition to commonphenotype of aniridia and despite normal neurological examination,absence of the pineal gland and interhemispheric brain anomalies wereobserved in all three index patients. The heterogeneity of PAX6mutations and brain anomalies are highlighted. This report emphasizesthe association between aniridia and brain anomalies with or withoutfunctional impact, such as neurodevelopment delay or auditorydysfunction.

[学科分类] 生物化学/生物物理