KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1.
KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1.
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DOI：
10.1016/j.ajo.2020.11.022
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发表时间：
2021-05
影响因子：
4.2
通讯作者：
Michaelides M
中科院分区：
文献类型：
--
作者：
Georgiou M;Robson AG;Fujinami K;Leo SM;Vincent A;Nasser F;Cabral De Guimarães TA;Khateb S;Pontikos N;Fujinami-Yokokawa Y;Liu X;Tsunoda K;Hayashi T;Vargas ME;Thiadens AAHJ;de Carvalho ER;Nguyen XT;Arno G;Mahroo OA;Martin-Merida MI;Jimenez-Rolando B;Gordo G;Carreño E;Ayuso C;Sharon D;Kohl S;Huckfeldt RM;Wissinger B;Boon CJF;Banin E;Pennesi ME;Khan AO;Webster AR;Zrenner E;Héon E;Michaelides M
在一组儿童和成人中研究kcnv2相关视网膜病变的遗传学、电生理学和临床病程。这是一项多中心国际临床队列研究。回顾临床记录和分子基因检测。结合国际标准，对全视场视网膜电图（ERG）记录进行审查和量化，并与对照组的年龄和记录进行比较。总共从117例患者中鉴定出230个疾病相关等位基因，对应75种不同的KCNV2变体，其中28种是新的。平均发病年龄为3.9岁。所有患者均在12岁前出现症状（范围0-11岁）。所有患者均出现视力下降，并伴有4种常见症状：色觉下降（78.6%）、畏光（53.5%）、夜盲症（43.6%）和眼球震颤（38.6%）。平均随访8.4年，平均最佳矫正视力（BCVA±SD）由最小分辨角的0.81±0.27对数降至0.90±0.31对数。全视场电图表现出典型的波形特征。定量评估显示，ERG振幅和峰值时间范围很广，与年龄相关的平均下降率与对照组没有区别。与对照组相比，暗适应0.01 ERG、暗适应10 ERG a波、la3.0 30hz和LA3 ERG b波的平均振幅分别降低了55%、21%、48%和74%。高峰时期显示出60年的稳定性。在kcnv2相关的视网膜病变中，全视场电图是诊断性的，并且与基本稳定的周围视网膜功能障碍一致。报告1强调了临床表型的严重性，并建立了一个大的患者队列，强调了对新疗法试验的未满足需求。目前的研究建立了规模最大、最具特征的kcnv2相关视网膜病变分子确诊患者队列。报告1强调了遗传背景，视网膜电图在广泛年龄范围内稳定性的证据，以及该疾病的严重表型。
To investigate genetics, electrophysiology, and clinical course of KCNV2-associated retinopathy in a cohort of children and adults. This was a multicenter international clinical cohort study. Review of clinical notes and molecular genetic testing. Full-field electroretinography (ERG) recordings, incorporating the international standards, were reviewed and quantified and compared with age and recordings from control subjects. In total, 230 disease-associated alleles were identified from 117 patients, corresponding to 75 different KCNV2 variants, with 28 being novel. The mean age of onset was 3.9 years old. All patients were symptomatic before 12 years of age (range, 0-11 years). Decreased visual acuity was present in all patients, and 4 other symptoms were common: reduced color vision (78.6%), photophobia (53.5%), nyctalopia (43.6%), and nystagmus (38.6%). After a mean follow-up of 8.4 years, the mean best-corrected visual acuity (BCVA ± SD) decreased from 0.81 ± 0.27 to 0.90 ± 0.31 logarithm of minimal angle of resolution. Full-field ERGs showed pathognomonic waveform features. Quantitative assessment revealed a wide range of ERG amplitudes and peak times, with a mean rate of age-associated reduction indistinguishable from the control group. Mean amplitude reductions for the dark-adapted 0.01 ERG, dark-adapted 10 ERG a-wave, and LA 3.0 30 Hz and LA3 ERG b-waves were 55%, 21%, 48%, and 74%, respectively compared with control values. Peak times showed stability across 6 decades. In KCNV2-associated retinopathy, full-field ERGs are diagnostic and consistent with largely stable peripheral retinal dysfunction. Report 1 highlights the severity of the clinical phenotype and established a large cohort of patients, emphasizing the unmet need for trials of novel therapeutics. The current study established the largest and most characterized cohort of molecularly confirmed patients with KCNV2-associated retinopathy. Report 1 highlights the genetic background, evidence of electroretinography stability over a broad age range, and the severe phenotype of the disease.
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影响因子：
1.6
作者：
Grigg, John R.;Holder, Graham E.;Jamieson, Robyn V.
通讯作者：
Jamieson, Robyn V.
影响因子：
3.4
作者：
Hart, Nathan S.;Mountford, Jessica K.;Carvalho, Livia S.
通讯作者：
Carvalho, Livia S.
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
4.7
作者：
Kuriyama S;Yaegashi N;Nagami F;Arai T;Kawaguchi Y;Osumi N;Sakaida M;Suzuki Y;Nakayama K;Hashizume H;Tamiya G;Kawame H;Suzuki K;Hozawa A;Nakaya N;Kikuya M;Metoki H;Tsuji I;Fuse N;Kiyomoto H;Sugawara J;Tsuboi A;Egawa S;Ito K;Chida K;Ishii T;Tomita H;Taki Y;Minegishi N;Ishii N;Yasuda J;Igarashi K;Shimizu R;Nagasaki M;Koshiba S;Kinoshita K;Ogishima S;Takai-Igarashi T;Tominaga T;Tanabe O;Ohuchi N;Shimosegawa T;Kure S;Tanaka H;Ito S;Hitomi J;Tanno K;Nakamura M;Ogasawara K;Kobayashi S;Sakata K;Satoh M;Shimizu A;Sasaki M;Endo R;Sobue K;Tohoku Medical Megabank Project Study Group T;Yamamoto M
通讯作者：
Yamamoto M
影响因子：
4.1
作者：
Khan, Arif O.;Alrashed, May;Alkuraya, Fowzan S.
通讯作者：
Alkuraya, Fowzan S.