Abstract：
UNASSIGNED: 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.
UNASSIGNED: Medical history, genetic testing, ocular examination, high-resolution retinal imaging including adaptive optics scanning light ophthalmoscopy (AOSLO), and functional assessments.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Medical history, genetic testing, ocular examination, high-resolution retinal imaging including adaptive optics scanning light ophthalmoscopy (AOSLO), and functional assessments.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■KCNV2基因中的致病变异与具有异常杆反应的视锥细胞营养不良有关，一种罕见的常染色体隐性视网膜营养不良。以前没有关于该疾病的低形态变异的报道。
■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检眼镜（AOSLO），和功能评估。
■一名16岁男性，患有轻度锥杆营养不良，表现为中心视力下降和畏光。遗传检测显示KCNV2中有两个变体，c.614_617dupAGCG（p.207AlafsTer166）和c.854T>G（p。Met285Arg),后者以前被认为是良性的。电生理评估显示与KCNV2视网膜病变相关的病理视网膜电图波形。光学相干层析成像显示离散焦点椭球区破裂，眼底自发荧光正常。对应于感光体完整性损失区域的非波导锥体在自适应光学扫描光检眼镜上可见。视网膜敏感性和固定相对保留，随访14个月后出现明显恶化。
■我们提供了功能和结构证据，证明M285R变体如果与功能丧失变体相关，则是致病的。据我们所知,这是KCNV2中报道的第一个低态等位基因.
■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检眼镜（AOSLO），和功能评估。
■一名16岁男性，患有轻度锥杆营养不良，表现为中心视力下降和畏光。遗传检测显示KCNV2中有两个变体，c.614_617dupAGCG（p.207AlafsTer166）和c.854T>G（p。Met285Arg),后者以前被认为是良性的。电生理评估显示与KCNV2视网膜病变相关的病理视网膜电图波形。光学相干层析成像显示离散焦点椭球区破裂，眼底自发荧光正常。对应于感光体完整性损失区域的非波导锥体在自适应光学扫描光检眼镜上可见。视网膜敏感性和固定相对保留，随访14个月后出现明显恶化。
■我们提供了功能和结构证据，证明M285R变体如果与功能丧失变体相关，则是致病的。据我们所知,这是KCNV2中报道的第一个低态等位基因.
