Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases
Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases
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DOI：
10.3346/jkms.2019.34.e161
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发表时间：
2019-06-03
影响因子：
4.5
通讯作者：
Woo, Se Joon
中科院分区：
文献类型：
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作者：
Kim, Min Seok;Joo, Kwangsic;Woo, Se Joon
背景资料：由于遗传性视网膜疾病（IRD）的遗传和表型异质性，在即将到来的基因治疗时代，确定致病基因是诊断和治疗的关键。到目前为止，在韩国还没有大规模的基因数据负责IRD。本研究的目的是确定遗传缺陷的分布在IRD患者在Korea.Methods：医疗记录和DNA样本86例临床诊断的IRD患者之间连续收集2011年7月和2015年5月。我们采用了新一代的测序策略结果：86例患者中38例获得分子诊断（44.2%）IRD患者：18/44（40.9%）视网膜色素变性（RP），8/22（36.4%）视锥细胞营养不良，6/7 Stargardt病（85.7%），1/1（100%）Best病，1/1（100%）Bardet-Biedl综合征，1/1（100%）先天性静止性夜盲，1/1（100%）无脉络膜，2/8（25%）其他黄斑营养不良。ABCA 4是与IRD相关的最常见的致病基因，并且负责引起Stargardt病（n = 6）、RP（n =1）和视锥细胞营养不良（n = 1）。特别是，在14例常染色体隐性遗传RP中发现4例（29%）EYS突变。Stargardt病的所有病例都有一个突变的ABCA 4基因与常染色体隐性trait.Conclusion：这项研究提供了分布的基因突变负责导致IRD在韩国患者。该数据将作为韩国IRD患者未来基因筛查和治疗的参考。
Background: Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea.Methods: Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD.Results: Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. ABCA4 was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n =1), and cone dystrophy (n = 1). In particular, mutations in EYS were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the ABCA4 gene with an autosomal recessive trait.Conclusion: This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients.