School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Int J Mol Sci. 2022 Aug 26;23(17):9707. doi: 10.3390/ijms23179707.
Cerebral visual impairments (CVIs) is an umbrella term that categorizes miscellaneous visual defects with parallel genetic brain disorders. While the manifestations of CVIs are diverse and ambiguous, molecular diagnostics stand out as a powerful approach for understanding pathomechanisms in CVIs. Nevertheless, the characterization of CVI disease cohorts has been fragmented and lacks integration. By revisiting the genome-wide and phenome-wide association studies (GWAS and PheWAS), we clustered a handful of renowned CVIs into five ontology groups, namely ciliopathies (Joubert syndrome, Bardet-Biedl syndrome, Alstrom syndrome), demyelination diseases (multiple sclerosis, Alexander disease, Pelizaeus-Merzbacher disease), transcriptional deregulation diseases (Mowat-Wilson disease, Pitt-Hopkins disease, Rett syndrome, Cockayne syndrome, X-linked alpha-thalassaemia mental retardation), compromised peroxisome disorders (Zellweger spectrum disorder, Refsum disease), and channelopathies (neuromyelitis optica spectrum disorder), and reviewed several mutation hotspots currently found to be associated with the CVIs. Moreover, we discussed the common manifestations in the brain and the eye, and collated animal study findings to discuss plausible gene editing strategies for future CVI correction.
脑视觉障碍 (CVI) 是一个总称，它将具有平行遗传脑疾病的各种视觉缺陷分类。虽然 CVI 的表现多种多样且不明确，但分子诊断是理解 CVI 发病机制的一种强有力方法。然而，CVI 疾病队列的特征描述一直是零散的，缺乏整合。通过重新审视全基因组和表型全基因组关联研究 (GWAS 和 PheWAS)，我们将一些著名的 CVI 聚类为五个本体组，即纤毛病 (Joubert 综合征、Bardet-Biedl 综合征、Alstrom 综合征)、脱髓鞘疾病 (多发性硬化症、Alexander 病、Pelizaeus-Merzbacher 病)、转录失调疾病 (Mowat-Wilson 病、Pitt-Hopkins 病、Rett 综合征、Cockayne 综合征、X 连锁α-地中海贫血智力迟钝)、过氧化物酶体功能障碍 (Zellweger 谱系障碍、Refsum 病)和通道病 (视神经脊髓炎谱系障碍)，并回顾了目前发现与 CVI 相关的几个突变热点。此外，我们讨论了大脑和眼睛的常见表现，并整理了动物研究结果，讨论了未来 CVI 矫正的合理基因编辑策略。
