标准与规范
ENGLISH ABSTRACT
Leber先天黑矇诊疗的中国专家共识(2023)
中国眼遗传病诊疗小组
中国眼科遗传联盟
作者及单位信息
·
DOI: 10.3760/cma.j.cn115989-20230523-00188
Chinese expert consensus on diagnosis and treatment of Leber congenital amaurosis (2023)
Chinese Hereditary Ocular Disease Diagnosis and Treatment Group
Chinese Hereditary Ocular Disease Alliance
Sui Ruifang
Authors Info & Affiliations
Chinese Hereditary Ocular Disease Diagnosis and Treatment Group
Chinese Hereditary Ocular Disease Alliance
Sui Ruifang
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
·
DOI: 10.3760/cma.j.cn115989-20230523-00188
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摘要

Leber先天性黑矇(LCA)是一种早发的会导致视功能严重损害的遗传性视网膜疾病,具有遗传异质性与表型多样性的特点,并表现出一定的基因型-临床表型相关性,其临床诊断和治疗均面临诸多挑战。一方面,LCA属于罕见病,发病率低,因此大多数眼科医师对LCA的临床表现尚未完全了解,故常常导致误诊或漏诊,延误治疗的最佳时机并影响患者的预后;另一方面,LCA基因治疗方法已经进入了临床试验阶段并取得了突破性进展,迫切要求广大眼科医师对LCA的表现及诊疗知识有更深入的认知,以便为患者提供治疗机会,改善患者的生活质量。目前由于国内眼科医师对LCA基本概念的欠缺而限制了对该病诊断和治疗方法的临床应用,中国眼科遗传联盟组织有关专家成立专家共识讨论小组,充分收集眼科医师在LCA诊疗过程中存在的主要问题,在认真复习国内外相关重要文献的基础上,结合专家组成员在相关临床研究和基础研究的成果以及临床实践经验,针对LCA的临床表现、诊断与鉴别诊断、基因检测策略以及治疗方案等问题撰写了《Leber先天黑矇诊疗的中国专家共识(2023)》,以指导中国广大眼科临床医师的医疗实践。

Leber先天性黑矇;早发严重型视网膜色素变性;基因治疗;基因型;临床表型;专家共识
ABSTRACT

Leber congenital amaurosis (LCA) is a group of early-onset hereditary retinal dystrophies characterized by genetic and phenotypic heterogeneity.LCA can cause severe visual impairment and shows a certain genotype-phenotype correlation, and its diagnosis and treatment face many challenges.On one hand, because LCA is a rare disease, most ophthalmologists are not familiar with its clinical manifestations, and misdiagnosis is very common.On the other hand, some clinical trials of gene therapy for LCA have been initiated, and breakthroughs have been achieved, requiring ophthalmologists to have a deeper understanding of the disease in order to make treatment available to more patients.Due to the lack of basic knowledge about LCA, the diagnosis and treatment methods for LCA are not widely used in China.The Chinese Hereditary Ocular Disease Alliance has organized relevant experts to form an expert consensus group, to fully collect the major challenges faced by ophthalmologists in diagnosing and treating LCA.Based on a careful review of relevant important literature at home and abroad, the achievements of the expert group members in relevant clinical and basic research, as well as their clinical practice experience, the Chinese Expert Consensus on the clinical manifestations, diagnosis and differential diagnosis, gene testing strategies, and treatment plans of LCA was completed to guide the medical practice of ophthalmologists in China.

Leber congenital amaurosis;Early-onset severe retinitis pigmentosa;Gene therapy;Genotype;Phenotype;Expert consensus
Sui Ruifang; Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China; Email: mocdef.3ab61iusfrh
引用本文

中国眼遗传病诊疗小组,中国眼科遗传联盟. Leber先天黑矇诊疗的中国专家共识(2023)[J]. 中华实验眼科杂志,2023,41(09):833-842.

DOI:10.3760/cma.j.cn115989-20230523-00188

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1 《Leber先天黑矇诊疗的中国专家共识(2023)》制定背景及方法
Leber先天性黑矇(Leber congenital amaurosis,LCA)是一种非常罕见的、具有严重致盲性的遗传性视网膜疾病。患者发病年龄早,且疾病对视功能的损害非常严重,给患者的视觉质量和生活质量造成极大影响。LCA具有非常显著的遗传异质性和临床异质性,即具有相同致病基因的患者其临床表型的差异可以很显著,而有些临床表现相似的患者其致病基因却完全不同 [ 1 ],故给LCA的临床诊断、鉴别诊断和基因治疗方案选择带来很大挑战。
LCA是首个进行基因治疗临床试验的眼科疾病,为这种既往认为不可逆致盲眼病患者带来了复明的希望,而准确的临床和基因诊断是精准进行基因治疗的基础。目前中国关于LCA诊疗的相关研究报道主要是病例报告和横断面研究结果,尚无针对我国LCA患者的诊疗规范,难以全面反映本病的特点和诊治要点,为LCA遗传学治疗的质量评价带来很大困难。如果临床医师对LCA临床表型特点认识不够,对该病基因诊断方法不了解,对诊断流程的知识欠缺,对遗传咨询方法学缺乏正确认识,对该病未来基因治疗方向和方法缺乏了解,则将给患者的医疗决策带来错误的指导,并且限制了我国在相关疾病遗传学诊疗和优生方面的深入科学研究。
鉴于目前我国临床医生对LCA的认知不足、诊断流程不规范、临床诊断及基因诊断误诊率高等问题,北京协和医院睢瑞芳教授组织成立了《Leber先天黑矇诊疗的中国专家共识(2023)》(简称《共识》)专家组,专家组成员由中国眼遗传病诊疗小组、中国眼科遗传联盟成员以及长期从事眼底病基础和临床研究的专家组成。目前关于LCA的诊疗,国内外尚无高等级循证证据的推荐意见。《共识》专家组在国内医疗机构进行广泛信息调查,从临床医师中收集LCA临床和基因诊疗中存在的困惑、疑难问题和瓶颈问题等,在检索和复习国内外相关研究文献、收集专家组成员的临床和基础研究成果的基础上,结合我国的临床实践,经专家组认真讨论将收集的意见凝练成LCA基本概念、临床表型特点及遗传学特点、常见致病基因、致病基因检测策略、诊断及鉴别诊断、治疗策略和预后以及临床咨询要点等科学问题,采用德尔菲法制定本专家共识。《共识》制定前由执笔专家撰写计划书(国际实践指南网平台可获得)并进行国际实践指南网注册(http://www.guidelines-registry.cn/)。专家组执笔成员在初步共识基础上撰写推荐意见,并将专家意见以电子邮件形式转发给各位成员,专家成员以背靠背的形式对推荐意见提出修改说明,根据国内外文献和核心组专家成员的临床经验对意见进行归纳整理。《共识》制定过程中充分注意专家遴选的专业性、与《共识》推荐意见相关知识的准确性和可靠性、专家对各条意见提出的独立性等。本共识自2022年7月开始,经过各位专家3轮背对背提出意见及充分讨论,历时10个月,最终形成本《共识》,旨在提升中国临床医生对LCA的认知能力和诊断水平,做到该病诊断的标准化,并且普及该病的基因治疗知识和遗传咨询知识。
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参考文献
[1]
睢瑞芳赵潺姜茹欣Leber先天黑矇的临床研究[J]中华眼底病杂志 200925(6)∶443446. DOI: 10.3760/cma.j.issn.1015-1005.2009.06.10 .
返回引文位置Google Scholar
百度学术
万方数据
Sui RF Zhao C Jiang RX et al. Clinical study on Leber congenital amaurosis[J]Chin J Ocul Fundus Dis 200925(6)∶443446. DOI: 10.3760/cma.j.issn.1015-1005.2009.06.10 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[2]
Wang H Wang X Zou X et al. Comprehensive molecular diagnosis of a large Chinese Leber congenital amaurosis cohort[J]Invest Ophthalmol Vis Sci 201556(6)∶36423655. DOI: 10.1167/iovs.14-15972 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Shen T Guan L Li S et al. Mutation analysis of Leber congenital amaurosis-associated genes in patients with retinitis pigmentosa[J]Mol Med Rep 201511(3)∶18271832. DOI: 10.3892/mmr.2014.2894 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
den Hollander AI Roepman R Koenekoop RK et al. Leber congenital amaurosis:genes,proteins and disease mechanisms[J]Prog Retin Eye Res 200827(4)∶391419. DOI: 10.1016/j.preteyeres.2008.05.003 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Xu Y Xiao X Li S et al. Molecular genetics of Leber congenital amaurosis in Chinese:new data from 66 probands and mutation overview of 159 probands[J]Exp Eye Res 20161499399. DOI: 10.1016/j.exer.2016.06.019 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
van der Spuy J Kim JH Yu YS et al. The expression of the Leber congenital amaurosis protein AIPL1 coincides with rod and cone photoreceptor development[J]Invest Ophthalmol Vis Sci 200344(12)∶53965403. DOI: 10.1167/iovs.03-0686 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Kirschman LT Kolandaivelu S Frederick JM et al. The Leber congenital amaurosis protein,AIPL1,is needed for the viability and functioning of cone photoreceptor cells[J]Hum Mol Genet 201019(6)∶10761087. DOI: 10.1093/hmg/ddp571 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Imanishi Y Batten ML Piston DW et al. Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye[J]J Cell Biol 2004164(3)∶373383. DOI: 10.1083/jcb.200311079 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Moise AR Golczak M Imanishi Y et al. Topology and membrane association of lecithin:retinol acyltransferase[J]J Biol Chem 2007282(3)∶20812090. DOI: 10.1074/jbc.M608315200 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Jin M Li S Moghrabi WN et al. Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium[J]Cell 2005122(3)∶449459. DOI: 10.1016/j.cell.2005.06.042 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Ikeda S He W Ikeda A et al. Cell-specific expression of tubby gene family members (tub,Tulp1,2,and 3) in the retina[J]Invest Ophthalmol Vis Sci 199940(11)∶27062712.
返回引文位置Google Scholar
百度学术
万方数据
[12]
Ikeda S Shiva N Ikeda A et al. Retinal degeneration but not obesity is observed in null mutants of the tubby-like protein 1 gene[J]Hum Mol Genet 20009(2)∶155163. DOI: 10.1093/hmg/9.2.155 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Milam AH Hendrickson AE Xiao M et al. Localization of tubby-like protein 1 in developing and adult human retinas[J]Invest Ophthalmol Vis Sci 200041(8)∶23522356.
返回引文位置Google Scholar
百度学术
万方数据
[14]
Sayer JA Otto EA O'Toole JF et al. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4[J]Nat Genet 200638(6)∶674681. DOI: 10.1038/ng1786 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Minegishi Y Sheng X Yoshitake K et al. CCT2 mutations evoke Leber congenital amaurosis due to chaperone complex instability[J/OL]Sci Rep 2016633742[2022-05-02]http://www.ncbi.nlm.nih.gov/pubmed/27645772. DOI: 10.1038/srep33742 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Chen X Wang X Jiang C et al. IFT52 as a Novel candidate for ciliopathies involving retinal degeneration[J]Invest Ophthalmol Vis Sci 201859(11)∶45814589. DOI: 10.1167/iovs.17-23351 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Henderson RH Williamson KA Kennedy JS et al. A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction[J]Mol Vis 20091524422447.
返回引文位置Google Scholar
百度学术
万方数据
[18]
中国眼遗传病诊疗小组中国眼科遗传联盟眼遗传病基因诊断方法专家共识[J]中华实验眼科杂志 201836(7)∶481488. DOI: 10.3760/cma.j.issn.2095-0160.2018.07.001 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Leber T Uber retinitis pigmentosa und angeborene amaurose[J]Graefe's Arch Clin Exp Ophthalmol 18691525.
返回引文位置Google Scholar
百度学术
万方数据
[20]
Kumaran N Moore AT Weleber RG et al. Leber congenital amaurosis/early-onset severe retinal dystrophy:clinical features,molecular genetics and therapeutic interventions[J]Br J Ophthalmol 2017101(9)∶11471154. DOI: 10.1136/bjophthalmol-2016-309975 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Heher KL Traboulsi EI Maumenee IH . The natural history of Leber's congenital amaurosis.Age-related findings in 35 patients[J]Ophthalmology 199299(2)∶241245. DOI: 10.1016/s0161-6420(92)31985-2 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Koenekoop RK . An overview of Leber congenital amaurosis:a model to understand human retinal development[J]Surv Ophthalmol 200449(4)∶379398.
返回引文位置Google Scholar
百度学术
万方数据
[23]
Foxman SG Heckenlively JR Bateman JB et al. Classification of congenital and early onset retinitis pigmentosa[J]Arch Ophthalmol 1985103(10)∶15021506. DOI: 10.1001/archopht.1985.01050100078023 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Varsányi B Wissinger B Kohl S et al. Clinical and genetic features of Hungarian achromatopsia patients[J]Mol Vis 2005119961001.
返回引文位置Google Scholar
百度学术
万方数据
[25]
Yuan S Qi R Fang X et al. Two novel PDE6C gene mutations in Chinese family with achromatopsia[J]Ophthalmic Genet 202041(6)∶591598. DOI: 10.1080/13816810.2020.1802762 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Cibis GW Fitzgerald KM . Optic nerve hypoplasia in association with brain anomalies and an abnormal electroretinogram[J]Doc Ophthalmol 199486(1)∶1122. DOI: 10.1007/BF01224624 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Weleber RG Tongue AC . Congenital stationary night blindness presenting as Leber's congenital amaurosis[J]Arch Ophthalmol 1987105(3)∶360365. DOI: 10.1001/archopht.1987.01060030080031 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Koenekoop RK Fishman GA Iannaccone A et al. Electroretinographic abnormalities in parents of patients with Leber congenital amaurosis who have heterozygous GUCY2D mutations[J]Arch Ophthalmol 2002120(10)∶13251330. DOI: 10.1001/archopht.120.10.1325 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Dharmaraj S Leroy BP Sohocki MM et al. The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations[J]Arch Ophthalmol 2004122(7)∶10291037. DOI: 10.1001/archopht.122.7.1029 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Lorenz B Wabbels B Wegscheider E et al. Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65[J]Ophthalmology 2004111(8)∶15851594. DOI: 10.1016/j.ophtha.2004.01.033 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Jacobson SG Cideciyan AV Aleman TS et al. Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination[J]Hum Mol Genet 200312(9)∶10731078. DOI: 10.1093/hmg/ddg117 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Jacobson SG Cideciyan AV Aleman TS et al. Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential[J]Ophthalmology 2007114(5)∶895898. DOI: 10.1016/j.ophtha.2006.10.028 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Zou X Fu Q Fang S et al. Phenotypic variability of recessive rdh12-associated retinal dystrophy[J]Retina 201939(10)∶20402052. DOI: 10.1097/IAE.0000000000002242 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
Bouzia Z Georgiou M Hull S et al. GUCY2D-Associated Leber Congenital Amaurosis:A Retrospective Natural History Study in Preparation for Trials of Novel Therapies. Am J Ophthalmol. 20202105970. doi: 10.1016/j.ajo.2019.10.019 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Simonelli F Ziviello C Testa F et al. Clinical and molecular genetics of Leber's congenital amaurosis:a multicenter study of Italian patients[J]Invest Ophthalmol Vis Sci 200748(9)∶42844290. DOI: 10.1167/iovs.07-0068 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Perrault I Hanein S Gerber S et al. Retinal dehydrogenase 12 (RDH12) mutations in leber congenital amaurosis[J]Am J Hum Genet 200475(4)∶639646. DOI: 10.1086/424889 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
Yzer S van den Born LI Schuil J et al. A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population[J]J Med Genet 200340(9)∶709713. DOI: 10.1136/jmg.40.9.709 .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Pasadhika S Fishman GA Stone EM et al. Differential macular morphology in patients with RPE65-,CEP290-,GUCY2D-,and AIPL1-related Leber congenital amaurosis[J]Invest Ophthalmol Vis Sci 201051(5)∶26082614. DOI: 10.1167/iovs.09-3734 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Zou X Yao F Liang X et al. De novo mutations in the cone-rod homeobox gene associated with leber congenital amaurosis in Chinese patients[J]Ophthalmic Genet 201536(1)∶2126. DOI: 10.3109/13816810.2013.827219 .
返回引文位置Google Scholar
百度学术
万方数据
[40]
Schwartz SG Wang X Chavis P et al. Vitamin A and fish oils for preventing the progression of retinitis pigmentosa[J/OL]Cochrane Database Syst Rev 20206(6)∶CD008428[2022-05-20]http://www.ncbi.nlm.nih.gov/pubmed/32573764. DOI: 10.1002/14651858.CD008428.pub3 .
返回引文位置Google Scholar
百度学术
万方数据
[41]
Vaz V Jardim da Silva L Geihs MA et al. Single and repeated low-dose UVB radiation exposures affect the visual system[J/OL]J Photochem Photobiol B 2020209111941[2022-05-20]http://www.ncbi.nlm.nih.gov/pubmed/32629396. DOI: 10.1016/j.jphotobiol.2020.111941 .
返回引文位置Google Scholar
百度学术
万方数据
[42]
Russell S Bennett J Wellman JA et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy:a randomised,controlled,open-label,phase 3 trial[J]Lancet 2017390(10097)∶849860. DOI: 10.1016/S0140-6736(17)31868-8 .
返回引文位置Google Scholar
百度学术
万方数据
[43]
Daich Varela M Cabral de Guimaraes TA Georgiou M et al. Leber congenital amaurosis/early-onset severe retinal dystrophy:current management and clinical trials[J]Br J Ophthalmol 2022106(4)∶445451. DOI: 10.1136/bjophthalmol-2020-318483 .
返回引文位置Google Scholar
百度学术
万方数据
[44]
Hussain RM Gregori NZ Ciulla TA et al. Pharmacotherapy of retinal disease with visual cycle modulators[J]Expert Opin Pharmacother 201819(5)∶471481. DOI: 10.1080/14656566.2018.1448060 .
返回引文位置Google Scholar
百度学术
万方数据
[45]
Redmond TM Yu S Lee E et al. Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle[J]Nat Genet 199820(4)∶344351. DOI: 10.1038/3813 .
返回引文位置Google Scholar
百度学术
万方数据
[46]
Scholl HP Moore AT Koenekoop RK et al. Safety and proof-of-concept study of oral QLT091001 in retinitis pigmentosa due to inherited deficiencies of retinal pigment epithelial 65 protein (RPE65) or lecithin:retinol acyltransferase (LRAT)[J/OL]PLoS One 201510(12)∶e0143846[2022-05-22]http://www.ncbi.nlm.nih.gov/pubmed/26656277. DOI: 10.1371/journal.pone.0143846 .
返回引文位置Google Scholar
百度学术
万方数据
[47]
Koenekoop RK Sui R Sallum J et al. Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations:an open-label phase 1b trial[J]Lancet 2014384(9953)∶15131520. DOI: 10.1016/S0140-6736(14)60153-7 .
返回引文位置Google Scholar
百度学术
万方数据
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A
睢瑞芳;北京协和医院眼科 北京协和医学院 中国医学科学院,北京 100730;Email: mocdef.3ab61iusfrh
B
http://www.guidelines-registry.cn/,PREPARE-2023CN193
C
http://www.guidelines-registry.cn,PREPARE-2023CN193
D
本《共识》制定过程中不存在任何利益冲突。
E
中国医学科学院医学与健康科技创新工程 (2021-I2M-1-003-202-01)
北京协和医院中央高水平医院临床科研专项 (LY22B1020003373)
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