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. 2023 Mar 28;14(4):813.
doi: 10.3390/genes14040813.

Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders

María Isabel Alvarez-Mora  1   2 , Laia Rodríguez-Revenga  1   2 , Meritxell Jodar  1   3 , Miriam Potrony  1   2 , Aurora Sanchez  1   2 , Celia Badenas  1   2 , Josep Oriola  1 , José Luis Villanueva-Cañas  4 , Esteban Muñoz  5 , Francesc Valldeoriola  5 , Ana Cámara  5 , Yaroslau Compta  5 , Mar Carreño  6 , María Jose Martí  5 , Raquel Sánchez-Valle  7   8 , Irene Madrigal  1   2
Affiliations

Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders

María Isabel Alvarez-Mora et al. Genes (Basel). .

Abstract

Neurological disorders (ND) are diseases that affect the brain and the central and autonomic nervous systems, such as neurodevelopmental disorders, cerebellar ataxias, Parkinson's disease, or epilepsies. Nowadays, recommendations of the American College of Medical Genetics and Genomics strongly recommend applying next generation sequencing (NGS) as a first-line test in patients with these disorders. Whole exome sequencing (WES) is widely regarded as the current technology of choice for diagnosing monogenic ND. The introduction of NGS allows for rapid and inexpensive large-scale genomic analysis and has led to enormous progress in deciphering monogenic forms of various genetic diseases. The simultaneous analysis of several potentially mutated genes improves the diagnostic process, making it faster and more efficient. The main aim of this report is to discuss the impact and advantages of the implementation of WES into the clinical diagnosis and management of ND. Therefore, we have performed a retrospective evaluation of WES application in 209 cases referred to the Department of Biochemistry and Molecular Genetics of the Hospital Clinic of Barcelona for WES sequencing derived from neurologists or clinical geneticists. In addition, we have further discussed some important facts regarding classification criteria for pathogenicity of rare variants, variants of unknown significance, deleterious variants, different clinical phenotypes, or frequency of actionable secondary findings. Different studies have shown that WES implementation establish diagnostic rate around 32% in ND and the continuous molecular diagnosis is essential to solve the remaining cases.

Keywords: Parkinson; ataxia; autism spectrum disorder; dystonia; epilepsy; neurodevelopmental disorders; neurological disorders; spastic paraplegia; whole exome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diagnostic rate of WES in patients with various neurological diseases. Blue bars indicate the percentage of cases in which a pathogenic variant has been detected; red bars indicate cases in which a VUS has been detected; and green bars indicate cases in which no responsible variant has been detected.
See this image and copyright information in PMC

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