Genetic Testing Leading to Early Identification of Childhood Ocular Manifestations of Usher Syndrome
Genetic Testing Leading to Early Identification of Childhood Ocular Manifestations of Usher Syndrome
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DOI：
10.1002/lary.29193
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发表时间：
2020-10-28
期刊：
影响因子：
2.6
通讯作者：
Chan, Dylan K.
中科院分区：
文献类型：
--
作者：
Brodie, Kara D.;Moore, Anthony T.;Chan, Dylan K.
目的听力损失基因板检测（HLGPT）作为确定儿童感音神经性听力损失（SNHL）病因的一线检测方法越来越受到重视。HLGPT的一个主要优势是在出现明显的综合征表型（可能影响治疗和咨询）之前，早期识别SNHL的综合征形式，尤其是Usher综合征。在这里，我们描述了早期眼部发现的儿童与临床非综合征SNHL确定HLGPT有两个变种相关的Usher syndrome.Methods共184名儿童，年龄1个月-15岁，在一个三级儿科儿童医院评估临床非综合征SNHL，进行下一代测序的150个基因参与听力损失。结果184例儿童中有18例存在Usher综合征相关基因的两种变异，包括MYO 7A、GPR 98（ADGRV 1）、USH 2A和PDZD 7。SNHL从中度到重度不等。29%的儿童进行了临床眼科评估被发现有以前未确定的视网膜异常视网膜成像或视网膜电图符合遗传性retinal degeneration.Conclusion在这个种族和种族多样性的儿童人群与明显的非综合征SNHL，HLGPT产生了很高的比例（10%）的儿童与两个变异的基因与Usher综合征。早期基因检测允许在视觉症状之前的阶段早期鉴定赋予Usher综合征诊断的变体。这使得更明智的遗传咨询，生殖计划，和感官缺陷干预。证据等级4级喉镜，2020
Objectives Hearing-loss gene panel testing (HLGPT) is increasingly accessible as a first-line test in determining the etiology of sensorineural hearing loss (SNHL) in children. A major advantage of HLGPT is early identification of syndromic forms of SNHL, especially Usher syndrome, prior to the development of overt syndromic phenotype, which may impact management and counseling. Here, we describe early ocular findings in children with clinically non-syndromic SNHL identified by HLGPT as having two variants associated with Usher Syndrome.Methods A total of 184 children, ages 1 month - 15 years of age, evaluated at one tertiary pediatric children's hospital for clinically non-syndromic SNHL, underwent next-generation sequencing of 150 genes involved in hearing loss. Children with two variants in genes associated with Usher syndrome were referred for evaluation by pediatric ophthalmology.Results A total of 18/184 tested children had two variants in Usher syndrome-associated genes, including MYO7A, GPR98 (ADGRV1), USH2A, and PDZD7. SNHL varied from moderate to profound. 29% of the children who underwent clinical ophthalmology evaluation were found to have previously unidentified retinal abnormalities on retinal imaging or electroretinography consistent with inherited retinal degeneration.Conclusion Among this ethnically and racially diverse pediatric population with apparently non-syndromic SNHL, HLGPT yielded a high proportion (10%) of children with two variants in genes associated with Usher syndrome. Early genetic testing allows early identification of variants conferring a diagnosis of Usher syndrome at a stage prior to visual symptoms. This allows for more informed genetic counseling, reproductive planning, and sensory deficit interventions.Level of Evidence Level 4 Laryngoscope, 2020