M285R KCNV2 低常等位基因个体的结构和功能特征。

IF 1.2 4区 医学 Q4 GENETICS & HEREDITY
Ophthalmic Genetics Pub Date : 2024-08-01 Epub Date: 2024-03-08 DOI:10.1080/13816810.2024.2324046
Thales A C de Guimaraes, Francesco Lai, Raffaella Colombatti, Giovanni Sato, Roberta Rizzo, Angelos Kalitzeos, Michel Michaelides
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引用次数: 0

摘要

背景:KCNV2基因的致病变体与 "视锥营养不良伴异常视杆细胞反应 "有关,这是一种罕见的常染色体隐性视网膜营养不良症。此前还没有关于该病低表型变异的报道:病史、基因检测、眼部检查、高分辨率视网膜成像(包括自适应光学扫描光眼底镜(AOSLO))和功能评估:一名患有轻度圆锥杆营养不良症的 16 岁男性患者出现中心视力下降和畏光。基因检测显示 KCNV2 存在两个变异:c.614_617dupAGCG (p.207AlafsTer166) 和 c.854T>G (p.Met285Arg),后者以前被认为是良性的。电生理评估显示了与 KCNV2 视网膜病变相关的病理视网膜电图波形。光学相干断层扫描显示,病灶椭圆形区断裂,而眼底自发荧光正常。在自适应光学扫描光眼底镜检查中,可以看到与感光器完整性丧失区域相对应的非导波锥体。视网膜的敏感性和固定性相对保持不变,但在 14 个月的随访后出现了明显的退化:我们提供的功能和结构证据表明,如果变异体 M285R 与功能缺失变异体相关联,则会致病。据我们所知,这是 KCNV2 中首次报道的低位等位基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Structural and functional characterization of an individual with the M285R KCNV2 hypomorphic allele.

Background: Disease-causing variants in the KCNV2 gene are associated with "cone dystrophy with supernormal rod responses," a rare autosomal recessive retinal dystrophy. There is no previous report of hypomorphic variants in the disease.

Material and methods: Medical history, genetic testing, ocular examination, high-resolution retinal imaging including adaptive optics scanning light ophthalmoscopy (AOSLO), and functional assessments.

Results: A 16-year-old male with mild cone-rod dystrophy presented with reduced central vision and photophobia. Genetic testing showed two variants in KCNV2, c.614_617dupAGCG (p.207AlafsTer166) and c.854T>G (p.Met285Arg), the latter which was previously considered benign. Electrophysiological assessment revealed the pathognomic electroretinogram waveforms associated with KCNV2-retinopathy. Optical coherence tomography showed discrete focal ellipsoid zone disruption, while fundus autofluorescence was normal. Non-waveguiding cones corresponding to areas of loss of photoreceptor integrity were visible on adaptive optics scanning light ophthalmoscopy. Retinal sensitivity and fixation were relatively preserved, with a demonstrable deterioration after 14 months of follow-up.

Conclusions: We provide functional and structural evidence that the variant M285R is disease-causing if associated with a loss-of-function variant. To the best of our knowledge, this is the first hypomorphic allele reported in KCNV2.

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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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