Pay more attention to several issues in genetic diagnosis for patients with inherited retinal diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

 Li Yang , Zhang Xin , Tian Lu

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing 100730, China;

Corresponding author：

Li Yang, Email: yilbio@163.com

Keywords：

Eye diseases, hereditary; Retinal diseases; Genetic testing; Molecular diagnostic techniques; Editorial

DOI：

10.3760/cma.j.cn511434-20220628-00387

Video：

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Inherited retinal diseases (IRD) are a group of genetic disorders with high genetic and clinical heterogeneity. Patients with IRD may have their clinical diagnosis confirmed by genetic testing. Over the past 30 years, rapid advances in molecular genetics have raised the disease-causing gene variant detection rate and the accuracy of genetic testing, which provide hope to patients. The genetic diagnosis of patients with IRD is complicated due to the overlapping clinical phenotypes, and the fact that different variants lead to different phenotypes and severity even of the same gene. It is very important to overall evaluate the clinical phenotype of patients, precisely select genetic testing methods, and reasonably define disease-causing genes and variants during genetic diagnosis, which can guide the patient's subsequent treatment and provide genetic counseling.

Citation： Li Yang, Zhang Xin, Tian Lu. Pay more attention to several issues in genetic diagnosis for patients with inherited retinal diseases. Chinese Journal of Ocular Fundus Diseases, 2022, 38(8): 617-620. doi: 10.3760/cma.j.cn511434-20220628-00387 Copy

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14.	Sangermano R, Khan M, Cornelis SS, et al. ABCA4 midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease[J]. Genome Res, 2018, 28(1): 100-110. DOI: 10.1101/gr.226621.117.
15.	Khan M, Arno G, Fakin A, et al. Detailed phenotyping and therapeutic strategies for intronic ABCA4 variants in Stargardt disease[J]. Mol Ther Nucleic Acids, 2020, 21: 412-427. DOI: 10.1016/j.omtn.2020.06.007.
16.	Zampaglione E, Kinde B, Place EM, et al. Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations[J]. Genet Med, 2020, 22(6): 1079-1087. DOI: 10.1038/s41436-020-0759-8.
17.	Ellingford JM, Barton S, Bhaskar S, et al. Whole genome sequencing increases molecular diagnostic yield compared with current diagnostic testing for inherited retinal disease[J]. Ophthalmology, 2016, 123(5): 1143-1150. DOI: 10.1016/j.ophtha.2016.01.009.
18.	Di Scipio M, Tavares E, Deshmukh S, et al. Phenotype driven analysis of whole genome sequencing identifies deep intronic variants that cause retinal dystrophies by aberrant exonization[J]. Invest Ophthalmol Vis Sci, 2020, 61(10): 36. DOI: 10.1167/iovs.61.10.36.
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1. Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases[J]. Prog Retin Eye Res, 2010, 29(5): 335-375. DOI: 10.1016/j.preteyeres.2010.03.004.
2. Vázquez-Domínguez I, Garanto A, Collin RWJ. Molecular therapies for inherited retinal diseases-current standing, opportunities and challenges[J]. Genes (Basel), 2019, 10(9): 654. DOI: 10.3390/genes10090654.
3. Eichler EE. Genetic variation, comparative genomics, and the diagnosis of disease[J]. N Engl J Med, 2019, 381(1): 64-74. DOI: 10.1056/NEJMra1809315.
4. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. DOI: 10.1038/gim.2015.30.
5. 王秋菊, 沈亦平, 陈少科, 等. 遗传变异分类标准与指南[J]. 中国科学 (生命科学), 2017, 47(6): 668-688. DOI: 10.1360/N052017-00099.Wang QJ, Shen YP, Chen SK, et al. Standards and guidelines for the interpretation of sequence variants[J]. Science in China (Series C), 2017, 47(6): 668-688. DOI: 10.1360/N052017-00099.
6. Abou Tayoun AN, Pesaran T, DiStefano MT, et al. Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant criterion[J]. Hum Mutat, 2018, 39(11): 1517-1524. DOI: 10.1002/humu.23626.
7. Lewis BP, Green RE, Brenner SE. Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans[J]. Proc Natl Acad Sci USA, 2003, 100(1): 189-192. DOI: 10.1073/pnas.0136770100.
8. Chang YF, Imam JS, Wilkinson MF. The nonsense-mediated decay RNA surveillance pathway[J]. Annu Rev Biochem, 2007, 76: 51-74. DOI: 10.1146/annurev.biochem.76.050106.093909.
9. Corradi Z, Salameh M, Khan M, et al. ABCA4 c. 859-25A>G, a frequent palestinian founder mutation affecting the intron 7 branchpoint, is associated with early-onset Stargardt disease[J]. Invest Ophthalmol Vis Sci, 2022, 63(4): 20. DOI: 10.1167/iovs.63.4.20.
10. Martin-Merida I, Sanchez-Alcudia R, Fernandez-San Jose P, et al. Analysis of the PRPF31 gene in Spanish autosomal dominant retinitis pigmentosa patients: a novel genomic rearrangement[J]. Invest Ophthalmol Vis Sci, 2017, 58(2): 1045-1053. DOI: 10.1167/iovs.16-20515.
11. Cremers FPM, Lee W, Collin RWJ, et al. Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations[J/OL]. Prog Retin Eye Res, 2020, 79: 100861[2020-04-09]. https://pubmed.ncbi.nlm.nih.gov/32278709/. DOI: 10.1016/j.preteyeres.2020.100861.
12. Tian L, Chen C, Song Y, et al. Phenotype-based genetic analysis reveals missing heritability of ABCA4-related retinopathy: deep intronic variants and copy number variations[J]. Invest Ophthalmol Vis Sci, 2022, 63(6): 5. DOI: 10.1167/iovs.63.6.5.
13. Parfitt DA, Lane A, Ramsden CM, et al. Identification and correction of mechanisms underlying inherited blindness in human iPSC-derived optic cups[J]. Cell Stem Cell, 2016, 18(6): 769-781. DOI: 10.1016/j.stem.2016.03.021.
14. Sangermano R, Khan M, Cornelis SS, et al. ABCA4 midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease[J]. Genome Res, 2018, 28(1): 100-110. DOI: 10.1101/gr.226621.117.
15. Khan M, Arno G, Fakin A, et al. Detailed phenotyping and therapeutic strategies for intronic ABCA4 variants in Stargardt disease[J]. Mol Ther Nucleic Acids, 2020, 21: 412-427. DOI: 10.1016/j.omtn.2020.06.007.
16. Zampaglione E, Kinde B, Place EM, et al. Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations[J]. Genet Med, 2020, 22(6): 1079-1087. DOI: 10.1038/s41436-020-0759-8.
17. Ellingford JM, Barton S, Bhaskar S, et al. Whole genome sequencing increases molecular diagnostic yield compared with current diagnostic testing for inherited retinal disease[J]. Ophthalmology, 2016, 123(5): 1143-1150. DOI: 10.1016/j.ophtha.2016.01.009.
18. Di Scipio M, Tavares E, Deshmukh S, et al. Phenotype driven analysis of whole genome sequencing identifies deep intronic variants that cause retinal dystrophies by aberrant exonization[J]. Invest Ophthalmol Vis Sci, 2020, 61(10): 36. DOI: 10.1167/iovs.61.10.36.
19. Tian L, Sun T, Xu K, et al. Screening of BEST1 gene in a Chinese cohort with best vitelliform macular dystrophy or autosomal recessive bestrophinopathy[J]. Invest Ophthalmol Vis Sci, 2017, 58(9): 3366-3375. DOI: 10.1167/iovs.17-21999.
20. Xiao T, Xie Y, Zhang X, et al. Variant profiling of a large cohort of 138 Chinese families with autosomal dominant retinitis pigmentosa[J/OL]. Front Cell Dev Biol, 2021, 8: 629994[2021-02-01]. https://pubmed.ncbi.nlm.nih.gov/33598457/. DOI:10.3389/fcell.2020.629994.

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Pay more attention to several issues in genetic diagnosis for patients with inherited retinal diseases

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