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青少年型开角型青光眼的遗传特征和基因研究进展

Advances in genetic characterization and genes of juvenile open angle glaucoma

发布日期：2024-05-22
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    [关键词]
    [摘要]

    青少年型开角型青光眼(JOAG)是原发性开角型青光眼(POAG)的一个亚型，具有较高的致残率，严重影响年轻患者的生活质量。研究发现JOAG有着多样化的遗传方式，虽然JOAG通常被认为是一种常染色体显性遗传疾病，但在特定人群中，常染色体隐性遗传同样存在。而JOAG的多变遗传倾向可能是由多个关键致病基因共同调控的结果，其中包括MYOC、CYP1B1和CPAMD8等代表性基因。这些基因的突变通常与眼部组织的多种生物学过程密切相关，主要包括细胞代谢调控、氧化应激反应以及程序性死亡的异常诱导。因此，深入研究JOAG相关的致病基因至关重要，这将为揭示该疾病的发生、发展及临床表型的具体遗传背景，并且为早期识别和筛查高风险人群提供有力依据。文章旨在重点关注JOAG的遗传特征和基因研究。通过系统性回顾相关文献，总结了与JOAG疾病相关的致病基因及其突变，并探讨其在JOAG研究领域未来发展中的潜在应用和价值，为JOAG的诊断和治疗提供有益的见解。

    [Key word]
    [Abstract]
    Juvenile open angle glaucoma(JOAG)is a subtype of primary open angle glaucoma(POAG)that severely affects the quality of life of young patients and has a high disability rate. While JOAG is commonly considered an autosomal dominant disease, it has been found to have a diverse mode of inheritance, including autosomal recessive inheritance in specific populations. The variable genetic predisposition of JOAG may be attributed to the co-regulation of several key disease-causing genes, such as MYOC, CYP1B1, and CPAMD8. Mutations in these genes are closely associated with various biological processes in ocular tissues, including cellular metabolic regulation, oxidative stress response, and abnormal induction of programmed death. Therefore, a comprehensive study of the causative genes associated with JOAG is crucial to understanding the specific genetic background of disease onset, progression, and clinical phenotype. This knowledge will provide a strong foundation for early identification and screening of high-risk populations. The objective of this review is to focus on the genetic characterization and genetic studies of JOAG. Through a systematic review of the relevant literature, we summarize the causative genes and their mutations associated with JOAG and explore their potential applications and value in advancing research in the field, aiming to provide valuable insights for the diagnosis and treatment of JOAG.
    [基金项目]
    国家自然科学基金资助项目(No.81770920); 眼科学国家重点实验室开放课题(No.303060202400383)
    \〖1\〗 Li F, Su YD, Lin FB, et al. A deep-learning system predicts glaucoma incidence and progression using retinal photographs. J Clin Invest, 2022,132(11):e157968.
    \〖2\〗 Kang JM, Tanna AP. Glaucoma. Med Clin North Am, 2021,105(3):493-510.
    \〖3\〗 Flores-Sánchez B, Tatham A. Acute angle closure glaucoma. Br J Hosp Med(Lond), 2019,80(12):C174-C179.
    \〖4\〗 陈智鑫. 青少年开角型青光眼的全外显子测序分析研究. 汕头大学, 2021.
    \〖5\〗 Warjri GB, Sidhu T, Kishan A, et al. Achieving low target intraocular pressures in severe glaucoma. Eur J Ophthalmol, 2021,31(6):3068-3073.
    \〖6\〗 Pasaoglu I, Basarir B. Comparison of anterior chamber angle parameters and iris structure of juvenile open-angle glaucoma and pigmentary glaucoma. Indian J Ophthalmol, 2022,70(2):558-563.
    \〖7\〗 Abdelrahman AM, Eltanamly RM, Elsanabary Z, et al. Optical coherence tomography angiography in juvenile open angle glaucoma: correlation between structure and perfusion. Int Ophthalmol, 2021,41(3):883-889.
    \〖8\〗 Sihota R, Sidhu T, Dada T. The role of clinical examination of the optic nerve head in glaucoma today. Curr Opin Ophthalmol, 2021,32(2):83-91.
    \〖9\〗 Cao Y, Lin HS, Mao HY, et al. Trend of glaucoma internal filtration surgeries in a tertiary hospital in China. Int J Ophthalmol, 2023,16(2):251-259.
    \〖10\〗 Schuster AK,Erb C, Hoffmann EM, et al. The diagnosis and treatment of glaucoma. Dtsch Arztebl Int, 2020,117(13):225-234.
    \〖11\〗 Seresirikachorn K, Thiamthat W, Annopawong K, et al. Treatment outcomes for juvenile open angle glaucoma in Thailand. J Glaucoma, 2023,32(11):976-982.
    \〖12\〗 Kwun Y, Lee EJ, Han JC, et al. Clinical characteristics of juvenile-onset open angle glaucoma. Korean J Ophthalmol, 2016,30(2):127-133.
    \〖13\〗 Kader MA, Devarajan B, Vijayan S, et al. Myocilin mutation N480K leads to early onset juvenile and adult-onset primary open angle glaucoma in a Six generation family. J Glaucoma, 2024,33(3):218-224.
    \〖14\〗 Vergaro A, Rezková L, Fichtl M, et al. Primary open-angle glaucoma due to mutations in the myoc gene. Cesk Slov Oftalmol, 2022,78(5):242-248.
    \〖15\〗 Falero-Perez J, Sorenson CM, Sheibani N. Retinal astrocytes transcriptome reveals Cyp1b1 regulates the expression of genes involved in cell adhesion and migration. PLoS One, 2020,15(4):e0231752.
    \〖16\〗 Wiggs JL. CPAMD8, a new gene for anterior segment dysgenesis and childhood glaucoma. Ophthalmology, 2020,127(6):767-768.
    \〖17\〗 Sudhakar V, Richardson RM. Gene therapy for neurodegenerative diseases. Neurotherapeutics, 2019,16(1):166-175.
    \〖18\〗 Gruzei C, Zhang JF, Bourne R. Testing the eligibility of glaucoma patients for potential gene therapy among a clinic population. Int Ophthalmol, 2022,42(3):785-797.
    \〖19\〗 曹静,唐喆,帅维维. 全球首个用于输血依赖的β-地中海贫血的基因疗法Zynteglo. 中国新药杂志, 2023,32(20):2029-2033.
    \〖20\〗 Fan W, Li W, Duan C, et al. Characterization of a novel mutation in the myoc gene in a chinese family with primary open-angle glaucoma. Mol Med Rep, 2020,22(4):3263-3270.
    \〖21\〗 Li XQ, Xiao XS, Li SQ, et al. Systemic genotype-phenotype analysis of MYOC variants based on exome sequencing and literature review. Asia Pac J Ophthalmol, 2021,10(2):173-182.
    \〖22\〗 Liuska PJ, Harju M, Kivelä TT, et al. Prevalence of MYOC risk variants for glaucoma in different populations. Acta Ophthalmol, 2021,99(7):e1090-e1097.
    \〖23\〗 Huang CK,Xie LJ, Wu ZG, et al. Detection of mutations in MYOC, OPTN, NTF4, WDR36 and CYP1B1 in Chinese juvenile onset open-angle glaucoma using exome sequencing. Sci Rep, 2018,8(1):4498.
    \〖24\〗 Yen YC, Yang JJ, Chou MC, et al. Identification of mutations in themyocilin(MYOC)gene in Taiwanese patients with juvenile-onset open-angle glaucoma. Mol Vis, 2007,13:1627-1634.
    \〖25\〗 Bayat B, Yazdani S, Alavi A, et al. Contributions of MYOC and CYP1B1 mutations to JOAG. Mol Vis, 2008,14:508-517.
    \〖26\〗 Svidnicki PV, Braghini CA, Costa VP, et al. Occurrence of MYOC and CYP1B1 variants in juvenile open angle glaucoma Brazilian patients. Ophthalmic Genet, 2018,39(6):717-724.
    \〖27\〗 Yao YH, Wang YQ, Fang WF, et al. A recurrent G367R mutation in MYOC associated with juvenile open angle glaucoma in a large Chinese family. Int J Ophthalmol, 2018,11(3):369-374.
    \〖28\〗 Moon S, Kim N, Lee J. Clinical and genetic analysis of Ser341ProMYOC variant in a Korean family with primary open angle glaucoma. Int J Ophthalmol, 2020,13(11):1689-1696.
    \〖29\〗 Lei L, Li SS, Liu XY, et al.The clinical feature of myocilin Y437H mutation in a Chinese family with primary open-angle glaucoma. Br J Ophthalmol, 2019,103(10):1524-1529.
    \〖30\〗 Zhang YH, Li S,Wen X, et al. MYOC promotes the differentiation of C2C12 cells by regulation of the TGF-β signaling pathways via CAV1. Biology, 2021,10(7):686.
    \〖31\〗 Alward WL. The genetics of open-angle glaucoma: the story of GLC1A and myocilin. Eye, 2000,14( Pt 3B):429-436.
    \〖32\〗 Yan X, Wu S, Liu Q, et al. Accumulation of Asn450Tyr mutant myocilin in ER promotes apoptosis of human trabecular meshwork cells. Mol Vis, 2020,26:563-573.
    \〖33\〗 Alward WLM, van der Heide C, Khanna CL, et al. Myocilin mutations in patients with normal-tension glaucoma. JAMA Ophthalmol, 2019,137(5):559-563.
    \〖34\〗 Wang HW, Li MZ, Zhang ZZ, et al. Physiological function of myocilin and its role in the pathogenesis of glaucoma in the trabecular meshwork(Review). Int J Mol Med, 2019,43(2):671-681.
    \〖35\〗 Dai A, Cheng X, Wang W, et al. A novel heterozygous c.733 T > G MYOC mutation associated with juvenile-onset open-angle glaucoma in a Chinese family. Eye(Lond), 2023,37(12):2488-2493.
    \〖36\〗 Yadav M, Yadav A, Bhardwaj A, et al. A rare optineurin mutation in an Indian family with coexistence of JOAG and PCG. Indian J Ophthalmol, 2023,71(8):3016-3023.
    \〖37\〗 Gupta V,Somarajan BI, Gupta S, et al. The mutational spectrum of Myocilin gene among familial versus sporadic cases of Juvenile onset open angle glaucoma. Eye, 2021,35:400-408.
    \〖38\〗 Tibrewal S, Ratna R, Gour A, et al. Clinical and molecular aspects of congenital aniridia - A review of current concepts. Indian J Ophthalmol, 2022,70(7):2280-2292.
    \〖39\〗 Falero-Perez J, Larsen M C, Teixeira L, et al. Targeted deletion of Cyp1b1 in pericytes results in attenuation of retinal neovascularization and trabecular meshwork dysgenesis. Trends Dev Biol, 2019,12:1-12.
    \〖40\〗 Song YS,Annalora AJ, Marcus CB, et al. Cytochrome P450 1B1:a key regulator of ocular iron homeostasis and oxidative stress. Cells, 2022,11(19):2930.
    \〖41\〗 Acharya M, Mookherjee S, Bhattacharjee A, et al. Primary role of CYP1B1 in Indian juvenile-onset POAG patients. Mol Vis, 2006,12:399-404.
    \〖42\〗 Alghamdi A, Aldossary W, Albahkali S, et al. The loss of microglia activities facilitates glaucoma progression in association with CYP1B1 gene mutation(p.Gly61Glu). PLoS One, 2020,15(11):e0241902.
    \〖43\〗 Haddad A,Ait Boujmia OK, El Maaloum L, et al. Meta-analysis of CYP1B1 gene mutations in primary congenital glaucoma patients. Eur J Ophthalmol, 2021,31(6):2796-2807.
    \〖44\〗 Abu-Amero KK, Morales J, Aljasim LA, et al. CYP1B1 mutations are a major contributor to juvenile-onset open angle glaucoma in Saudi Arabia. Ophthalmic Genet, 2015,36(2):184-187.
    \〖45\〗 Chouiter L, Nadifi S. Analysis of CYP1B1 gene mutations in patients with primary congenital glaucoma. J Pediatr Genet, 2017,6(4):205-214.
    \〖46\〗 Bonet-Fernández JM, Aroca-Aguilar JD, Corton M, et al. CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix. Hum Genet, 2020,139(10):1209-1231.
    \〖47\〗 Li X, Sun W, XiaoX, et al. Biallelic variants in CPAMD8 are associated with primary open-angle glaucoma and primary angle-closure glaucoma. Br J Ophthalmol, 2022,106(12):1710-1715.
    \〖48\〗 Ylikotila P, Sipilä J, Alapirtti T, et al. Association of biallelic RFC1 expansion with early-onset Parkinson's disease. Eur J Neurol, 2023,30(5):1256-1261.
    \〖49\〗 di Donato N, Guerrini R, Billington CJ, et al. Monoallelic and biallelic mutations in RELN underlie a graded series of neurodevelopmental disorders. Brain, 2022,145(9):3274-3287.
    \〖50\〗 Othman BA,Ong JE, Dumitrescu AV. Biallelic optic atrophy 1(OPA1)related disorder-case report and literature review. Genes, 2022,13(6):1005.
    \〖51\〗 Siggs OM, Souzeau E, Taranath DA, et al. Biallelic CPAMD8 variants are a frequent cause of childhood and juvenile open-angle glaucoma. Ophthalmology, 2020,127(6):758-766.
    \〖52\〗 Ma AL,Yousoof S, Grigg JR, et al. Revealing hidden genetic diagnoses in the ocular anterior segment disorders. Genet Med, 2020,22(10):1623-1632.
    \〖53\〗 de-la-Torre A, Silva-Aldana CT, Muñoz-Ortiz J, et al. Uveitis and multiple sclerosis: potential common causal mutations. Mol Neurobiol, 2019,56(12):8008-8017.
    \〖54\〗 Hollmann AK, Dammann I, Wemheuer WM, et al. Morgagnian cataract resulting from a naturally occurring nonsense mutation elucidates a role of CPAMD8 in mammalian lens development. PLoS One, 2017,12(7):e0180665.
    \〖55\〗 Cheong SS,Hentschel L, Davidson AE, et al. Mutations in CPAMD8 cause a unique form of autosomal-recessive anterior segment dysgenesis. Am J Hum Genet, 2016,99(6):1338-1352.
    \〖56\〗 Adam MP, Feldman J, Mirzaa GM,et al. Nail-Patella Syndrome.GeneReviews® \〖Internet\〗Seattle(WA): University of Washington, Seattle; 1993-2024.
    \〖57\〗 Jiménez-Moreno N, Kollareddy M, Stathakos P, et al. ATG8-dependent LMX1B-autophagy crosstalk shapes human midbrain dopaminergic neuronal resilience. J Cell Biol, 2023,222(5):e201910133.
    \〖58\〗 Haro E, Petit F, Pira CU, et al. Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity. Nat Commun, 2021,12(1):5533.
    \〖59\〗 Harita Y, Kitanaka S, Isojima T, et al. Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy. Pediatr Nephrol, 2017,32(10):1845-1850.
    \〖60\〗 Tolman NG, Balasubramanian R, Macalinao DG, et al. Genetic background modifies vulnerability to glaucoma-related phenotypes in Lmx1b mutant mice. Dis Models Mech, 2021,14(2):dmm046953.
    \〖61\〗 Willoughby CE, Chan LL, Herd S, et al.Defining the pathogenicity of optineurin in juvenile open-angle glaucoma. Invest Ophthalmol Vis Sci, 2004,45(9):3122-3130.
    \〖62\〗 Qiu YP, Wang JC, Li H, et al. Emerging views of OPTN(optineurin)function in the autophagic process associated with disease. Autophagy, 2022,18(1):73-85.
    \〖63\〗 Limagne E, Nuttin L, Thibaudin M, et al. MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells. Cancer Cell, 2022,40(2):136-152.e12.
    \〖64\〗 Liu X, Hou M, Zhang S, et al. Neuroprotective effects of bone marrow Sca-1(+)cells against age-related retinal degeneration in OPTN E50K mice. Cell Death Dis, 2021,12(6):613.
    \〖65\〗 Chu CT. Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases. Neurobiol Dis, 2019,122:23-34.
    \〖66\〗 Evans CS,Holzbaur ELF. Autophagy and mitophagy in ALS. Neurobiol Dis, 2019,122:35-40.
    \〖67\〗 Park J, Kim M, Park CK, et al. Molecular analysis of myocilin and optineurin genes in Korean primary glaucoma patients. Mol Med Rep, 2016,14(3):2439-2448.
    \〖68\〗 Sayyad Z, Kaveti S, Bhattacharjee D, et al. A glaucoma-associated OPTN polymorphism, M98K sensitizes retinal cells to endoplasmic reticulum stress and tumour necrosis factor Α. FEBS J, 2023,290(12):3110-3127.
    \〖69\〗 Yau T, Park JW, Finn RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma(CheckMate 459):a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol, 2022,23(1):77-90.
    \〖70\〗 Zhang SQ,Shao ZB, Liu XN, et al. The E50K optineurin mutation impacts autophagy-mediated degradation of TDP-43 and leads to RGC apoptosis in vivo and in vitro. Cell Death Discov, 2021,7(1):49.
    \〖71\〗 Xiao XQ, Huang CK, Cao YJ, et al. Exome sequencing reveals a heterozygous OAS3 mutation in a Chinese family with juvenile-onset open-angle glaucoma. Invest Ophthalmol Vis Sci, 2019,60(13):4277-4284.
    \〖72\〗 Gupta V,Somarajan BI, Gupta S, et al. A new association of PAX6 variation with Juvenile onset open angle glaucoma. J Hum Genet, 2023,68(5):355-358.
    \〖73\〗 Yang X, Sun NN, Zhao ZN, et al. Coinheritance of OLFM2 and SIX6 variants in a Chinese family with juvenile-onset primary open-angle glaucoma: a case report. World J Clin Cases, 2021,9(3):697-706.
    \〖74\〗 Huang XB, Li ML,Guo XM, et al. Mutation analysis of seven known glaucoma-associated genes in Chinese patients with glaucoma. Invest Ophthalmol Vis Sci, 2014,55(6):3594-3602.
    \〖75\〗 Nussinov R, Tsai CJ, Jang H. Protein ensembles link genotype to phenotype. PLoS Comput Biol, 2019,15(6):e1006648.
    \〖76\〗 Xue BK, Sartori P, Leibler S. Environment-to-phenotype mapping and adaptation strategies in varying environments. Proc Natl Acad Sci U S A, 2019,116(28):13847-13855.
    \〖77\〗 Springelkamp H, Iglesias AI, Cuellar-Partida G, et al. ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure. Hum Mol Genet, 2015,24(9):2689-2699.
    \〖78\〗 Wiggs JL, Yaspan BL, Hauser MA, et al. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS Genet, 2012,8(4):e1002654.
    \〖79\〗 Gharahkhani P, Burdon KP, Fogarty R, et al. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. Nat Genet, 2014,46(10):1120-1125.
    \〖80\〗 Thorleifsson G, Walters GB, Hewitt AW, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet, 2010,42(10):906-909.
    \〖81\〗 Bailey JN, Loomis SJ, Kang JH, et al. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet, 2016,48(2):189-194.
    \〖82\〗 Youngblood H, Hauser MA, Liu YT. Update on the genetics of primary open-angle glaucoma. Exp Eye Res, 2019,188:107795.
    \〖83\〗 Hakim A, Guido B,Narsineni L, et al. Gene therapy strategies for glaucoma from IOP reduction to retinal neuroprotection: Progress towards non-viral systems. Adv Drug Deliv Rev, 2023,196:114781.
    \〖84\〗 Jia LY, Gong B, Pang CP, et al. Correction of the disease phenotype of myocilin-causing glaucoma by a natural osmolyte. Invest Ophthalmol Vis Sci, 2009,50(8):3743-3749.
    \〖85\〗 Amador C, Shah R,Ghiam S, et al. Gene therapy in the anterior eye segment. Curr Gene Ther, 2022,22(2):104-131.
    \〖86\〗 Bulcha JT, Wang Y, Ma H, et al. Viral vector platforms within the gene therapy landscape. Signal Transduct Target Ther, 2021,6(1):53.
    \〖87\〗 Tan JK, Xiao Y, Liu G, et al. Evaluation of trabecular meshwork-specific promoters in vitro and in vivo using scAAV2 vectors expressing C3 transferase. Int J Ophthalmol, 2023,16(8):1196-1209.
    \〖88\〗 Wu WY, Tang LS, D'Amore PA, et al. Application of CRISPR-Cas9 in eye disease. Exp Eye Res, 2017,161:116-123.
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