Department of Ophthalmology, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, University Hospital "Sveti Duh", Zagreb, Croatia.
Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
Ophthalmic Genet. 2023 Jun;44(3):276-280. doi: 10.1080/13816810.2022.2106496. Epub 2022 Jul 29.
It is of utmost importance to define the molecular diagnosis of patients with retinitis pigmentosa (RP) due to existing targeted therapeutic option: voretigene neparvovec.We provide clinical evidence for pathogenicity reclassification of variants of uncertain significance (VUSs) c.1580A>G (p.His527Arg).
A case report of a 10-year-old boy with progressive vision loss. The patient manifested disease highly suggestive of retinal dystrophy: nyctalopia, fairly good central vision, severely depressed full-field electroretinography responses and complete loss of peripheral fundus aut ofluorescence.
Invitae Inherited Retinal Disorders Panel identified likely pathogenic mutation c.499G>T (p.Asp167Tyr) and c.1580A>G (p.His527Arg), variant of uncertain significance. Segregation analysis confirmed that these variants are in .
We conclude that the variant c.1580A>G (p.His527Arg) has contributed to the pathologic phenotype, demonstrating its significance clearly in the case presented, and should be reclassified according to the criteria of evidence as pathogenic. Therefore, patients with this specific variant in homozygous or compound heterozygous form would likely benefit from genetic treatment based on recombinant adeno-associated virus vector, providing a working gene to act in place of a mutated RPE65 gene.
由于存在靶向治疗选择：voretigene neparvovec，对视网膜色素变性 (RP) 患者进行分子诊断至关重要。我们为变异的致病性重新分类提供了临床证据不确定意义 (VUSs) c.1580A>G (p.His527Arg)。
一名 10 岁男孩进行性视力丧失的病例报告。患者表现出高度提示视网膜营养不良的疾病：夜盲症、相当好的中心视力、全视野视网膜电图反应严重降低和周边眼底自发荧光完全丧失。
Invitae 遗传性视网膜疾病小组确定了可能的致病性突变 c.499G>T (p.Asp167Tyr) 和 c.1580A>G (p.His527Arg)，变体意义不确定。 分离分析证实这些变体在.
我们得出结论，变体 c.1580A>G (p.His527Arg) 导致了病理表型，在提出的病例中清楚地表明了其意义，根据证据标准应重新归类为致病性。因此，具有这种特定变体纯合或复合杂合形式的患者可能会受益于基于重组腺相关病毒载体的基因治疗，提供一个工作基因来替代突变的 RPE65 基因。
