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. 2020 Dec 18:11:591434.
doi: 10.3389/fgene.2020.591434. eCollection 2020.

Clinical Utility of Exome Sequencing and Reinterpreting Genetic Test Results in Children and Adults With Epilepsy

Yong-Li Jiang  1 , Changgeng Song  1 , Yuanyuan Wang  1 , Jingjing Zhao  1 , Fang Yang  1 , Qiong Gao  1 , Xiuxiu Leng  1 , Yulin Man  1 , Wen Jiang  1
Affiliations

Clinical Utility of Exome Sequencing and Reinterpreting Genetic Test Results in Children and Adults With Epilepsy

Yong-Li Jiang et al. Front Genet. .

Abstract

The clinical utility of genetic testing for epilepsy has been enhanced with the advancement of next-generation sequencing (NGS) technology along with the rapid updating of publicly available databases. The aim of this study was to evaluate the diagnostic yield of NGS and assess the value of reinterpreting genetic test results in children and adults with epilepsy. We performed genetic testing on 200 patients, including 82 children and 118 adults. The results were classified into three categories: positive, inconclusive, or negative. The reinterpretation of inconclusive results was conducted in April 2020. Overall, we identified disease-causing variants in 12% of the patients in the original analysis, and 14.5% at reinterpretation. The diagnostic yield for adults with epilepsy was similar to that for children (11 vs. 19.5%, p = 0.145). After reinterpretation, 9 of the 86 patients who initially had inconclusive results obtained a clinically significant change in diagnosis. Among these nine revised cases, five obtained positive diagnoses, representing a diagnosis rate of 5.8% (5/86). Manual searches for additional evidence of pathogenicity for candidate variants and updated patient clinical information were the main reasons for diagnostic reclassification. This study emphasizes the diagnostic potential of combining NGS and reinterpretation of inconclusive genetic test reports in children and adults with epilepsy.

Keywords: adults; epilepsy; genetic testing; next-generation sequencing; reinterpretation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The distribution of mutated genes, mode of inheritance, and variant type for cases with a positive molecular diagnosis. (A) y-axis: the number of patients; x-axis: genes carrying presumed pathogenic variants. (B) AD, autosomal dominant; AR, autosomal recessive; XL, X-linked disorders.
FIGURE 2
FIGURE 2
Flow chart of the initial analysis and reinterpretation.
FIGURE 3
FIGURE 3
Results reinterpreted in the study. (A) Number of reclassified variants; (B) evidence for change.
See this image and copyright information in PMC

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