低形态CDHR1变体可能导致视网膜色素变性,视锥功能相对保留。

IF 1.2 4区 医学 Q4 GENETICS & HEREDITY
Ophthalmic Genetics Pub Date : 2024-04-01 Epub Date: 2023-09-20 DOI:10.1080/13816810.2023.2255265
Soma Farag, Imran H Yusuf, Maria Kaukonen, Laura J Taylor, Peter Charbel Issa, Robert E MacLaren
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引用次数: 0

摘要

目的:与CDHR1双等位基因变异相关的色素性视网膜炎(RP)很少报道,也没有详细的表型数据。与CDHR1中双等位基因缺失变异相关的视锥-视杆营养不良相比,RP意味着中央凹视锥的相对保存。我们假设RP可能与一个或多个亚形态CDHR1等位基因相关。材料和方法:一例48岁CDHR1相关RP伴低形态错义变体c.562患者的回顾性报告 G> A,p.(Gly188Ser)和一种影响典型剪接受体位点的新的、未报道的变体(c.784-1 G> C)。进行了临床检查、多模式视网膜成像、视网膜电图、视野测试和中视显微检查8 相隔多年。还进行了Scotopic微量血液测定。检测变体的DNA序列背景,以确定理论CRISPR-Cas9碱基编辑策略。结果:患者在35岁时出现 年,有12年的夜虫病病史。他的最佳矫正视力为20/20。临床表现、多模式视网膜成像研究、视网膜电图和中视显微视野测量是进行性棒锥营养不良(即经典RP)的典型表现。在CDHR1相关的视锥-视杆营养不良患者中,中心视野内没有出现预期的暗点。Scotopic显微镜检查显示黄斑视锥对视杆功能有一定的保护作用,尽管两者都严重受损。确定了一种合适的CRISPR腺嘌呤碱基编辑器,理论上可以纠正错义变体c.562 G> A,p.(Gly188Ser)。结论:CDHR1相关RP在假定的亚形态等位基因存在的情况下表现出锥体功能的相对保留,可能被认为是亚形态疾病表型。需要进一步的工作来确定决定疾病表型的修饰因子,因为黄斑营养不良,相对保留杆,也可能发生低形态CDHR1等位基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hypomorphic CDHR1 variants may result in retinitis pigmentosa with relative preservation of cone function.

Purpose: Retinitis pigmentosa (RP) associated with biallelic variants in CDHR1 has rarely been reported, and detailed phenotyping data are not available. RP implies relative preservation of foveal cones, when compared to cone-rod dystrophy associated with biallelic null variants in CDHR1. We hypothesize that RP may occur in association with one or more hypomorphic CDHR1 alleles.

Materials and methods: Retrospective report of a 48-year-old patient with CDHR1-associated RP with a hypomorphic missense variant c.562 G>A, p. (Gly188Ser) and a novel, unreported variant affecting a canonical splice acceptor site (c.784-1 G>C). Clinical examination, multimodal retinal imaging, electroretinography, visual field testing, and mesopic microperimetry were undertaken 8 years apart. Scotopic microperimetry was also performed. The DNA sequence context of the variants was examined to identify theoretical CRISPR-Cas9 base-editing strategies.

Results: The patient presented at 35 years with a 12-year history of nyctalopia. His best corrected visual acuity was 20/20. Clinical presentation, multimodal retinal imaging studies, electroretinography, and mesopic microperimetry were typical of a progressive rod-cone dystrophy (i.e. classic RP). There were no scotomas within the central field as would be expected at this age in CDHR1-associated cone-rod dystrophy. Scotopic microperimetry suggested some preservation of macular cone over rod function, although both were severely impaired. A suitable CRISPR adenine base editor was identified that could theoretically correct the missense variant c.562 G>A, p. (Gly188Ser).

Conclusions: CDHR1-associated RP shows a relative preservation of cone function in the presence of a presumed hypomorphic allele and may be considered a hypomorphic disease phenotype. Further work is required to identify modifying factors that determine disease phenotype since macular dystrophy, with relative sparing of rods, may also occur with hypomorphic CDHR1 alleles.

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来源期刊
Ophthalmic Genetics
Ophthalmic Genetics 医学-眼科学
CiteScore
2.40
自引率
8.30%
发文量
126
审稿时长
>12 weeks
期刊介绍: Ophthalmic Genetics accepts original papers, review articles and short communications on the clinical and molecular genetic aspects of ocular diseases.
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