Clinical and mutational signatures of CRB1-associated retinopathies: a multicentre study.

IF 3.5 2区 医学 Q2 GENETICS & HEREDITY Journal of Medical Genetics Pub Date : 2024-11-04 DOI:10.1136/jmg-2024-110289
Mo-Ying Wang, Feng-Juan Gao, Yu-Qiao Ju, Lin-Ying Guo, Cong Duan, Qing Chang, Ting Zhang, Ge-Zhi Xu, Hui Du, Yuan Zong, Xin Huang
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Abstract

Background: To delineate the clinical and mutational signatures of patients with CRB1-associated retinopathies.

Methods: This multicentre retrospective cohort study involved 40 patients with CRB1 mutations and 40 age-matched and gender-matched inherited retinal diseases (IRDs). The detailed phenotyping and genotyping characteristics and genotype‒phenotype correlations of the patients were analysed.

Results: The mean age of CRB1 cohort was 27.33±14.63 years. Results showed that yellowish geographic macular degeneration (66.67%), small white or yellow dots (65.6%), hyperopia (62.5%), abnormally laminated retina (61.61%), epiretinal membrane (60.6%) and nummular pigment deposits (50%) were the most common signatures in patients with CRB1 mutations. These clinical signatures were notably more prevalent among CRB1 patients than among individuals in other IRD group (p<0.001). Early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) patients are more likely to present these signatures than retinitis pigmentosa (RP) and macular dystrophy (MD) patients. Furthermore, a significant reduction in central foveal thickness coupled with pronounced thickening of the peripheral retina was observed more distinctly in patients with EOSRD/LCA (p<0.001). The choroidal thickness was not significantly altered compared to the normal controls, but was markedly reduced in the other IRD groups (p<0.001). 55 pathogenic variants were identified, 20 of which were novel. Null mutations were associated with EOSRD/LCA patients, and missense mutations were more prevalent in MD and RP patients.

Conclusions: Key clinical and mutational signatures were demonstrated in this study, providing a comprehensive update on CRB1-associated retinopathies that will aid in diagnosis and lay the foundation for future therapeutic studies.

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CRB1相关视网膜病变的临床和突变特征:一项多中心研究。
背景:研究CRB1相关视网膜病变患者的临床和突变特征:方法:这项多中心回顾性队列研究涉及 40 名 CRB1 基因突变患者和 40 名年龄和性别匹配的遗传性视网膜疾病(IRD)患者:这项多中心回顾性队列研究涉及40名CRB1突变患者和40名年龄和性别匹配的遗传性视网膜疾病(IRD)患者。研究分析了患者的详细表型和基因分型特征以及基因型与表型之间的相关性:结果:CRB1组群的平均年龄为(27.33±14.63)岁。结果显示,黄斑变性(66.67%)、小白点或黄点(65.6%)、远视(62.5%)、视网膜异常层(61.61%)、视网膜外膜(60.6%)和麻木性色素沉积(50%)是CRB1基因突变患者最常见的临床特征。这些临床特征在 CRB1 患者中的发病率明显高于其他 IRD 组别患者(结论:本研究显示了关键的临床和突变特征,为 CRB1 相关视网膜病变提供了全面的最新信息,有助于诊断并为未来的治疗研究奠定基础。
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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
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