Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease
Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease
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DOI：
10.1016/j.ophtha.2017.02.005
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发表时间：
2017-07-01
期刊：
影响因子：
13.7
通讯作者：
Sergouniotis, Panagiotis I.
中科院分区：
文献类型：
--
作者：
Taylor, Rachel L.;Parry, Neil R. A.;Sergouniotis, Panagiotis I.
目的：评估遗传性视网膜疾病（IRD）儿童人群中基因检测的临床实用性。设计：单中心回顾性病例系列。参与者：85名诊断为孤立性或综合征性IRD的无关儿童，他们在2014年1月至2016年7月期间接受临床基因检测。参与者进行了详细的眼科检查，并在适当的情况下进行了电诊断测试（EDT）和畸形评估。使用人类表型本体学术语记录眼部和眼外特征。随后，多基因面板测试（105或177个IRD相关基因）在经认可的诊断实验室中进行，随后进行临床变异判读.主要结果测量：基因检测的诊断率和临床有用性.结果：总体而言，78.8%的患者（n = 67）接受了可能的分子诊断;其中7.5%（n = 5）为常染色体显性遗传病，25.4%（n = 17）为X连锁遗传病，67.2%（n = 45）为常染色体隐性遗传病。在另外5.9%的患者（n = 5）中，确定了单个杂合ABCA 4变体;所有这些参与者都具有与ABCA 4视网膜病变一致的临床特征谱。大多数参与者（84.7%; n = 72）接受了EDT，其中81.9%（n = 59）的患者接受了可能的分子诊断。本队列中最常突变的基因是CACNA 1F和ABCA 4，分别占诊断的14.9%（n = 10）和11.9%（n = 8）。值得注意的是，在许多情况下，基因检测有助于区分静止进行性IRD亚型，并建立一个准确的诊断及时fashion.Conclusions：多基因面板测试指出，在84.7%的儿童IRD的分子诊断。研究人群中的诊断率显著高于先前报道的CIDIRD队列。类似于本文所述的方法有望成为儿科眼科护理的标准组成部分。我们建议在有临床和/或电生理结果提示IRD的儿童的诊断途径中早期引入基因检测。(C)2017年美国眼科学会
Purpose: To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD).Design: Single-center retrospective case series.Participants: Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016.Methods: Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation.Main Outcome Measures: Diagnostic yield and clinical usefulness of genetic testing.Results: Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion.Conclusions: Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology. We propose the introduction of genetic testing early in the diagnostic pathway in children with clinical and/or electrophysiologic findings, suggestive of IRD. (C) 2017 by the American Academy of Ophthalmology