Department of Ophthalmology, Copenhagen University Hospital-Rigshospitalet, 2600 Glostrup, Denmark.
Department of Clinical Genetics, Copenhagen University Hospital-Rigshospitalet, 2100 Copenhagen, Denmark.
Genes (Basel). 2023 Mar 10;14(3):690. doi: 10.3390/genes14030690.
Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are being developed, but the current evidence is still conflicting regarding possible progression over time, and there is no clear genotype-phenotype correlation. This natural history study aimed to further explore the course of disease and potential clinical differences between various genotypes. The retrospective design allowed for the study of a large cohort with a long follow-up. Patients were identified from the Danish national registries. If not already available, genetic analysis was offered to the patient. Clinical data from 1945-2022 were retrieved from medical records and included best-corrected visual acuity (BCVA), color vision, refractive error, nystagmus, visual fields and fundoscopic findings. We identified variants believed to be disease causing in five of the known achromatopsia genes: ; ; ; and ; and novel variants were identified in and . Progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in and The results indicate that myopia could be more frequently occurring with variants in , and and support the evidence that achromatopsia is a predominantly stationary condition with respect to BCVA. Although a clear genotype-phenotype correlation can still not be concluded, there may be differences in phenotypical characteristics with variants in different genes.
全色盲是一种罕见的先天性疾病，由于视锥细胞功能障碍导致色盲、视力下降、眼球震颤和畏光。新的治疗方法正在开发中，但目前关于疾病随时间进展的可能性的证据仍然存在冲突，并且没有明确的基因型-表型相关性。这项自然史研究旨在进一步探讨疾病的过程和各种基因型之间可能存在的临床差异。回顾性设计允许对大量具有长期随访的患者进行研究。患者是从丹麦国家登记册中确定的。如果尚未进行基因分析，则向患者提供基因分析。从病历中检索了 1945 年至 2022 年的临床数据，包括最佳矫正视力 (BCVA)、色觉、屈光不正、眼球震颤、视野和眼底检查结果。我们在五个已知的全色盲基因中鉴定出了被认为是致病的变异体： ; ; ; 和 ;，并在 和 中发现了新的变异体。在 58 名患者中，有 3 名患者仅归因于全色盲的 BCVA 逐渐恶化。在 和 中发现了进行性表型。结果表明，在 、 和 中，近视可能更常与变异体相关，并且支持全色盲在 BCVA 方面主要是静止状态的证据。尽管仍然无法得出明确的基因型-表型相关性，但不同基因的变异体可能存在表型特征的差异。
