Abstract：
BACKGROUND: The objective of this study was to investigate the clinical characteristics and genetic spectrum of adult-onset cone/cone-rod dystrophy (AOCD/AOCRD) in Korean individuals.
METHODS: This is a single-center, retrospective cross-sectional study. We analyzed 22 individuals with genetically confirmed cone dystrophy, with symptoms beginning after 30 years of age. All patients underwent comprehensive ophthalmic and electrophysiological examinations. Exome sequencing of 296 genes associated with inherited retinal disease was performed. The clinical features of patients with AOCD/AOCRD and the causative genes and variants detected by exome sequencing were analyzed.
RESULTS: The median age at the first visit was 52 years (range, 31-76 years), and the most common initial symptom was reduced visual acuity. In most cases, fundus photography showed a bull\'s eye pattern with foveal sparing, consistent with perifoveal photoreceptor loss on optical coherence tomography. We identified disease-causing variants in six genes: RP1, CRX, CDHR1, PROM1, CRB1, and GUCY2D. Pathogenic variants in RP1, CRX, and CDHR1 were identified in 77% of the AOCD/AOCRD cases, including p.Cys1399LeufsTer5, p.Arg1933Ter, and p.Ile2061SerfsTer12 in RP1; p.Ter300GlnextTer118 in CRX; and p.Glu201Lys in CDHR1. No characteristic imaging differences were observed for any of the causative genes. Most of the RP1-related AOCD/AOCRD cases showed a decreased amplitude only in the photopic electroretinogram (ERG), whereas CRX-related AOCD/AOCRD cases showed a slightly decreased amplitude in both the scotopic and photopic ERGs.
CONCLUSIONS: In case of visual impairment with bull\'s eye pattern of RPE atrophy recognized after the middle age, a comprehensive ophthalmic examination and genetic test should be considered, with the possibility of AOCD/AOCRD in East Asians.
METHODS: This is a single-center, retrospective cross-sectional study. We analyzed 22 individuals with genetically confirmed cone dystrophy, with symptoms beginning after 30 years of age. All patients underwent comprehensive ophthalmic and electrophysiological examinations. Exome sequencing of 296 genes associated with inherited retinal disease was performed. The clinical features of patients with AOCD/AOCRD and the causative genes and variants detected by exome sequencing were analyzed.
RESULTS: The median age at the first visit was 52 years (range, 31-76 years), and the most common initial symptom was reduced visual acuity. In most cases, fundus photography showed a bull\'s eye pattern with foveal sparing, consistent with perifoveal photoreceptor loss on optical coherence tomography. We identified disease-causing variants in six genes: RP1, CRX, CDHR1, PROM1, CRB1, and GUCY2D. Pathogenic variants in RP1, CRX, and CDHR1 were identified in 77% of the AOCD/AOCRD cases, including p.Cys1399LeufsTer5, p.Arg1933Ter, and p.Ile2061SerfsTer12 in RP1; p.Ter300GlnextTer118 in CRX; and p.Glu201Lys in CDHR1. No characteristic imaging differences were observed for any of the causative genes. Most of the RP1-related AOCD/AOCRD cases showed a decreased amplitude only in the photopic electroretinogram (ERG), whereas CRX-related AOCD/AOCRD cases showed a slightly decreased amplitude in both the scotopic and photopic ERGs.
CONCLUSIONS: In case of visual impairment with bull\'s eye pattern of RPE atrophy recognized after the middle age, a comprehensive ophthalmic examination and genetic test should be considered, with the possibility of AOCD/AOCRD in East Asians.
摘要：
背景：本研究的目的是调查韩国人成年发病的锥/锥-杆营养不良（AOCD/AOCRD）的临床特征和遗传谱。
方法：这是一个单中心，回顾性横断面研究。我们分析了22名基因证实患有视锥细胞营养不良的个体，症状在30岁以后开始。所有患者均接受全面的眼科和电生理检查。对与遗传性视网膜疾病相关的296个基因进行外显子组测序。分析AOCD/AOCRD患者的临床特征以及通过外显子组测序检测到的致病基因和变异。
结果：首次就诊的中位年龄为52岁（范围，31-76岁），最常见的初始症状是视力下降。在大多数情况下,眼底摄影显示了带有中央凹保留的牛眼图案，与光学相干断层扫描的中央凹周围感光体丢失一致。我们确定了六个基因的致病变异：RP1，CRX，CDHR1、PROM1、CRB1和GUCY2D。RP1、CRX、在77%的AOCD/AOCRD病例中发现了CDHR1，包括p.Cys1399LeufsTer5,p.Arg1933Ter,RP1中的p.Ile2061SerfsTer12；CRX中的p.Ter300GlnextTer118；CDHR1中的p.Glu201Lys。对于任何致病基因均未观察到特征性成像差异。大多数与RP1相关的AOCD/AOCRD病例仅在明视视网膜电图（ERG）中显示振幅降低，而与CRX相关的AOCD/AOCRD病例在暗视和明视ERG中均显示出幅度略有降低。
结论：在中年后识别出RPE萎缩的牛眼模式的视力障碍的情况下，应考虑全面的眼科检查和基因测试，在东亚人中存在AOCD/AOCRD的可能性。
方法：这是一个单中心，回顾性横断面研究。我们分析了22名基因证实患有视锥细胞营养不良的个体，症状在30岁以后开始。所有患者均接受全面的眼科和电生理检查。对与遗传性视网膜疾病相关的296个基因进行外显子组测序。分析AOCD/AOCRD患者的临床特征以及通过外显子组测序检测到的致病基因和变异。
结果：首次就诊的中位年龄为52岁（范围，31-76岁），最常见的初始症状是视力下降。在大多数情况下,眼底摄影显示了带有中央凹保留的牛眼图案，与光学相干断层扫描的中央凹周围感光体丢失一致。我们确定了六个基因的致病变异：RP1，CRX，CDHR1、PROM1、CRB1和GUCY2D。RP1、CRX、在77%的AOCD/AOCRD病例中发现了CDHR1，包括p.Cys1399LeufsTer5,p.Arg1933Ter,RP1中的p.Ile2061SerfsTer12；CRX中的p.Ter300GlnextTer118；CDHR1中的p.Glu201Lys。对于任何致病基因均未观察到特征性成像差异。大多数与RP1相关的AOCD/AOCRD病例仅在明视视网膜电图（ERG）中显示振幅降低，而与CRX相关的AOCD/AOCRD病例在暗视和明视ERG中均显示出幅度略有降低。
结论：在中年后识别出RPE萎缩的牛眼模式的视力障碍的情况下，应考虑全面的眼科检查和基因测试，在东亚人中存在AOCD/AOCRD的可能性。
