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电生理学指导的遗传特征分析最大化了爱尔兰儿科遗传性视网膜变性人群的分子诊断。

Electrophysiology-Guided Genetic Characterisation Maximises Molecular Diagnosis in an Irish Paediatric Inherited Retinal Degeneration Population.

机构信息

Mater Clinical Ophthalmic Genetics Unit, The Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland.

Ophthalmology Department, Children's University Hospital, Temple Street, D01 XD99 Dublin, Ireland.

出版信息

Genes (Basel). 2022 Mar 29;13(4):615. doi: 10.3390/genes13040615.

Abstract

Inherited retinal degenerations (IRDs) account for over one third of the underlying causes of blindness in the paediatric population. Patients with IRDs often experience long delays prior to reaching a definitive diagnosis. Children attending a tertiary care paediatric ophthalmology department with phenotypic (i.e., clinical and/or electrophysiologic) evidence suggestive of IRD were contacted for genetic testing during the SARS-CoV-2-19 pandemic using a "telegenetics" approach. Genetic testing approach was panel-based next generation sequencing (351 genes) via a commercial laboratory (Blueprint Genetics, Helsinki, Finland). Of 70 patient samples from 57 pedigrees undergoing genetic testing, a causative genetic variant(s) was detected for 60 patients (85.7%) from 47 (82.5%) pedigrees. Of the 60 genetically resolved IRD patients, 5% ( = 3) are eligible for approved therapies () and 38.3% ( = 23) are eligible for clinical trial-based gene therapies including ( = 2), ( = 3), ( = 6), ( = 5) and ( = 7). The early introduction of genetic testing in the diagnostic/care pathway for children with IRDs is critical for genetic counselling of these families prior to upcoming gene therapy trials. Herein, we describe the pathway used, the clinical and genetic findings, and the therapeutic implications of the first systematic coordinated round of genetic testing of a paediatric IRD cohort in Ireland.

摘要

遗传性视网膜退行性疾病(IRDs)占儿科人群失明的三分之一以上。IRD 患者在获得明确诊断之前往往需要长时间的等待。在 SARS-CoV-2-19 大流行期间,采用“远程遗传学”方法,对在三级儿科眼科就诊的具有表型(即临床和/或电生理)提示 IRD 证据的儿童进行遗传检测。遗传检测方法是通过商业实验室(芬兰赫尔辛基的 Blueprint Genetics)进行基于面板的下一代测序(351 个基因)。在对 57 个家系的 70 个患者样本进行基因检测后,在 47 个(82.5%)家系的 60 个患者(85.7%)中检测到了致病基因突变。在 60 名遗传性视网膜退行性疾病患者中,5%(=3)有资格接受已批准的治疗方法(),38.3%(=23)有资格接受临床试验基因治疗,包括 (=2)、 (=3)、 (=6)、 (=5)和 (=7)。在患有 IRD 的儿童的诊断/护理途径中尽早引入基因检测,对于即将进行的基因治疗试验前对这些家庭进行遗传咨询至关重要。在此,我们描述了爱尔兰首例对儿科 IRD 队列进行系统协调的基因检测的途径、临床和遗传发现以及治疗意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7c/9033125/ed28163de90b/genes-13-00615-g001.jpg

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