Diagnostic and clinical utility of comprehensive multigene panel testing for patients with neuropathy

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Journal of the Peripheral Nervous System Pub Date : 2024-08-14 DOI:10.1111/jns.12651
Jennifer Roggenbuck, Ana Morales, Colin A. Ellis, Laynie Dratch, Molly Stetler, Christopher A. Tan, Brianna Bucknor, Kathryn E. Hatchell, Swaroop Aradhya, Edward D. Esplin, Yi-Lee Ting, Steven S. Scherer
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Abstract

Background and Aims

Prior to next-generation sequencing (NGS), the evaluation of a patient with neuropathy typically consisted of screening for acquired causes, followed by clinical genetic testing of PMP22, MFN2, GJB1, and MPZ in patients with a positive family history and symptom onset prior to age 50. In this study, we examined the clinical utility of NGS in a large cohort of patients analyzed in a commercial laboratory.

Methods

A cohort of 6849 adult patients underwent clinician-ordered peripheral neuropathy multigene panel testing ranging from 66 to 111 genes that included NGS and intragenic deletion/duplication analysis.

Results

A molecular diagnosis was identified for 8.4% of the cohort (n = 573/6849). Variants in PMP22, MFN2, GJB1, MPZ, and TTR accounted for 73.8% of molecular diagnoses. Results had potential clinical actionability for 398 (69.5%) patients. Our results suggest that 225/573 (39.3%) of molecular diagnoses and 113/398 (28.4%) of clinical interventions would have been missed if the testing approach had been restricted to older guidelines.

Interpretation

Our results highlight the need for expanded genetic testing guidelines that account for the increased number of genes associated with hereditary neuropathy, address the overlap of acquired and hereditary neuropathy, and provide broader access to genetic diagnosis for patients.

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神经病变患者多基因综合面板检测的诊断和临床实用性。
背景和目的:在使用新一代测序技术(NGS)之前,对神经病患者的评估通常包括筛查获得性病因,然后对有阳性家族史且在 50 岁之前发病的患者进行 PMP22、MFN2、GJB1 和 MPZ 的临床基因检测。在本研究中,我们在商业实验室分析的一大批患者中考察了 NGS 的临床实用性:6849 名成年患者接受了临床医生要求的周围神经病变多基因组检测,检测范围从 66 个基因到 111 个基因,包括 NGS 和基因内缺失/重复分析:结果:8.4%的患者(n = 573/6849)得到了分子诊断。PMP22、MFN2、GJB1、MPZ 和 TTR 的变异占分子诊断的 73.8%。398例(69.5%)患者的结果具有潜在的临床可操作性。我们的结果表明,如果检测方法仅限于旧版指南,将错过 225/573 例(39.3%)分子诊断和 113/398 例(28.4%)临床干预:我们的研究结果凸显了扩大基因检测指南范围的必要性,这些指南应考虑到与遗传性神经病相关基因数量的增加,解决获得性和遗传性神经病的重叠问题,并为患者提供更广泛的基因诊断途径。
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来源期刊
CiteScore
6.10
自引率
7.90%
发文量
45
审稿时长
>12 weeks
期刊介绍: The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.
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