Newly identified paired box 6 mutation of variant familial aniridia: Congenital iris ectropion with foveal hypoplasia.
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ABSTRACT:
SUBMITTER: Kim WJ
PROVIDER: S-EPMC5369295 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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Newly identified paired box 6 mutation of variant familial aniridia: Congenital iris ectropion with foveal hypoplasia.
Kim Woo Jin WJ Kim Jong Ha JH Cho Nam Chun NC
Indian journal of ophthalmology 20170101 1
Congenital aniridia is a kind of eye disease characterized by complete or partial hypoplasia of the iris and is associated with other ocular anomalies including corneal opacity, glaucoma, and foveal hypoplasia. Heterozygous mutation of paired box 6 (PAX6) gene was identified in most cases of aniridia, with iatrogenic mutations accounting for about two-third of the cases and chromosomal rearrangements accounting for the other one-third. We report rare cases of variant aniridia, congenital iris ec ...[more]
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Project description:Purpose:To investigate the association between PAX6 genotype and macular morphology in congenital aniridia. Methods:The study included 37 participants (15 males) with congenital aniridia (aged 10-72 years) and 58 age-matched normal controls (18 males). DNA was isolated from saliva samples. PAX6 exons, intron/exon junctions, and known regulatory regions were amplified in PCR and sequenced. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect larger deletions or duplications in PAX6 or known cis-regulatory regions. Spectral-domain optical coherence tomography images were acquired and segmented semiautomatically. Mean thicknesses were calculated for inner and outer retinal layers within the macula along nasal and temporal meridians. Results:Mutations in PAX6 or regulatory regions were found in 97% of the participants with aniridia. Foveal hypoplasia was observed in all who had a mutation within the PAX6 gene. Aniridic eyes had thinner outer retinal layers than controls, but with large between-individual variation (mean ± SD, 156.3 ± 32.3 µm vs 210.8 ± 12.3 µm, P < 0.001). Parafoveal and perifoveal inner and outer retinal layers were thinner in aniridia. Participants with mutations in noncoding PAX6 regions had thicker foveal outer retinal layers than those with mutations in the PAX6 coding regions (P = 0.04) and showed signs of postnatal development and maturation. Mutations outside the PAX6 gene were associated with the mildest retinal phenotypes. Conclusions:PAX6 mutations are associated with significant thinning of macular inner and outer retinal layers, consistent with misdirected retinal development resulting in abnormal foveal formation and reduced number of neurons in the macula, with mutations in PAX6 coding regions giving the worst outcome.
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