PAX6 Genotypic and Retinal Phenotypic Characterization in Congenital Aniridia
PAX6 Genotypic and Retinal Phenotypic Characterization in Congenital Aniridia
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DOI：
10.1167/iovs.61.5.14
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发表时间：
2020-05-01
影响因子：
4.4
通讯作者：
Neitz, Maureen
中科院分区：
文献类型：
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作者：
Pedersen, Hilde R.;Baraas, Rigmor C.;Neitz, Maureen
目的.探讨PAX 6基因型与先天性无虹膜黄斑形态的关系。该研究包括37名先天性无虹膜（10-72岁）的参与者（15名男性）和58名年龄匹配的正常对照（18名男性）。从唾液样本中分离DNA。PCR扩增PAX 6外显子、内含子/外显子连接和已知调控区并测序。进行多重连接依赖性探针扩增（MLPA）以检测PAX 6或已知顺式调节区域中的较大缺失或重复。光谱域光学相干断层扫描图像采集和半自动分割。计算黄斑内沿沿着鼻侧和颞侧视网膜的内外视网膜层的平均厚度。PAX 6或调控区的突变在97%的无虹膜参与者中被发现。在所有PAX 6基因突变的患者中均观察到黄斑中心凹发育不全。无虹膜眼的视网膜外层比对照组薄，但个体间差异较大（平均值± SD，156.3 ± 32.3 μ m vs 210.8 ± 12.3 μ m，P < 0.001）。无虹膜组视网膜内外层厚度较薄。PAX 6非编码区突变的参与者比PAX 6编码区突变的参与者有更厚的中央凹外视网膜层（P = 0.04），并显示出出生后发育和成熟的迹象。PAX 6基因以外的突变与最轻微的视网膜表型相关。PAX 6突变与黄斑内视网膜层和外视网膜层的显著变薄相关，与导致异常中央凹形成和黄斑中神经元数量减少的错误视网膜发育一致，PAX 6编码区的突变产生最差结果。
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 cisregulatory 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 mu m vs 210.8 +/- 12.3 mu m, 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.