MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
J Med Genet. 2024 May 21;61(6):605-612. doi: 10.1136/jmg-2023-109670.
Cerebral visual impairment (CVI) is the most common form of paediatric visual impairment in developed countries. CVI can arise from a host of genetic or acquired causes, but there has been limited research to date on CVI in the context of genetic disorders.
We carried out a retrospective analysis of genotypic and phenotypic data for participants with CVI within the DECIPHER database and 100 000 Genomes Project (100KGP).
158 individuals with CVI were identified across both cohorts. Within this group, pathogenic or likely pathogenic sequence variants in 173 genes were identified. 25 of these genes already have known associations with CVI, while the remaining 148 are candidate genes for this phenotype. Gene ontology analysis of the CVI gene sets from both DECIPHER and 100KGP suggests that CVI has a similar degree of genetic heterogeneity to other neurodevelopmental phenotypes, and a strong association with genetic variants converging on ion channels and receptor functions. Individuals with a monogenic disorder and CVI have a higher frequency of epilepsies and severe neurodisability than individuals with a monogenic disorder but not CVI.
This study supports the availability of genetic testing for individuals with CVI alongside other neurodevelopmental difficulties. It also supports the availability of ophthalmological screening for individuals with genetic diagnoses linked to CVI. Further studies could elaborate on the links between specific genetic disorders, visual maturation and broader neurodevelopmental characteristics.
在发达国家，脑性视觉障碍（CVI）是儿童视力障碍中最常见的形式。CVI 可能由多种遗传或获得性原因引起，但迄今为止，针对遗传疾病背景下的 CVI 研究有限。
我们对 DECIPHER 数据库和 10 万基因组计划（100KGP）中 CVI 参与者的基因型和表型数据进行了回顾性分析。
在两个队列中，共鉴定出 158 名 CVI 个体。在这组患者中，发现了 173 个基因中的致病性或可能致病性序列变异。其中 25 个基因已与 CVI 相关，而其余 148 个基因是该表型的候选基因。来自 DECIPHER 和 100KGP 的 CVI 基因集的基因本体分析表明，CVI 与其他神经发育表型具有相似程度的遗传异质性，并且与离子通道和受体功能的遗传变异密切相关。患有单基因疾病和 CVI 的个体比患有单基因疾病但无 CVI 的个体更易发生癫痫和严重神经功能障碍。
本研究支持对 CVI 及其他神经发育障碍患者进行基因检测，也支持对与 CVI 相关的基因诊断患者进行眼科筛查。进一步的研究可以详细阐述特定遗传疾病、视觉成熟度和更广泛的神经发育特征之间的联系。
