Clinical utility of a 377 gene custom next-generation sequencing epilepsy panel

Abstract

Epilepsy is one of the most common neurological disorders with about 500 genes thought to be involved across the phenotypic spectrum (Busch et al. 2014; Ran et al. 2014), which includes monogenic, multigenic, epistatic and pleiotropic phenotype manifestations (Busch et al. 2014; Thomas et al. 2014), driving the need for a comprehensive diagnostic test. Next-generation sequencing (NGS) allows for the simultaneous investigation of a large number of genes, making it a very attractive option for a condition as diverse as epilepsy at a low cost compared to traditional Sanger sequencing (Lemke et al. 2012; Németh et al. 2013). Our 377 gene epilepsy NGS test was developed to include genes known to cause or have published association with epilepsy and seizure-related disorders. Given the scale of information that is generated, the efficacy of an NGS panel depends on a number of factors, including the genes present on the panel, prebioinformatic and postbioinformatic analysis protocols, as well as reporting criteria, prompting the current study, a retrospective analysis of 305 cases tested for the epilepsy panel.

Horizon Scan Of Clinical Laboratories Offering Pharmacogenetic Testing

“…17 The movement away from traditional single-gene tests is not unique to PGx: Multigene panel tests have been developed for carrier screening (to identify whether one or both parents carry a copy of a mutated gene to determine their risk of having a child with a genetic condition), cancer susceptibility, cardiovascular disease, and developmental disabilities. 18,19 In 2012 a PGx genotyping array that included 117 genes was developed by investigators at Stanford University and the University of Florida. 20 In 2014 the PGRN-Seq capture panel was developed, which includes 84 genes associated with PGx pathways.…”

Identifying the educational needs of physicians in pediatric epilepsy in order to improve care: results from a needs assessment in Germany, Spain, and the United States

“…A low level of knowledge of the new 2017 ILAE classification guide, as reported by a majority of neuropediatrician participants, could be explained by its relatively recent publication (Fisher et al, 2017) A trend towards the use of genetic testing in identifying the etiology of certain epilepsy types has also emerged in the literature in recent years. There is an increase in scientific knowledge of the genes associated with epilepsy, as well as an increase in recommendations that physicians should perform genetic screening for all drug-resistant forms of epilepsy (Ream and Patel, 2015;Wilmshurst et al, 2015;Bevilacqua et al, 2017). In fact, the hope that genetic testing would help achieve better treatment (i.e.…”

Diagnostic gene sequencing panels: from design to report—a technical standard of the American College of Medical Genetics and Genomics (ACMG)

“…Panels for phenotypically related disorders can increase the likelihood of identifying an underlying genetic cause and may be preferred to exome or genome sequencing to maximize target coverage and avoid secondary findings. 1,2 Due to differences in decision-making processes in the absence of clear professional standards, genes included on similar disease-focused panels vary between laboratories. With the ability to sequence multiple genes simultaneously, it is imperative to evaluate critically the validity of gene-disease associations prior to test design.…”