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The International Journal of the Royal Society of Thailand
Volume XI - 2019

Since the last decade, the advent of NGS has led to the diagnosis in patients with
various neurological disorders (Klein and Foroud, 2017; Rexach et al., 2019). This
technology allows for easy and rapid expansion of the analyzed genes beyond the

initial hypothesis. The discovery of novel disease genes has increased exponentially
and led to an understanding of the disease pathomechanism. Precision treatment
based on precision diagnosis results in improved clinical outcomes. Molecular
information also makes it possible for clinicians to give a more precise and
appropriate genetic counseling and offer prenatal diagnosis (Amarinthnukrowh
et al., 2010; Kuptanon et al., 2019; Boonsimma et al., 2020a; Boonsimma et al.,
2020b). In this review, we describe the use of NGS in the diagnosis of neurological
disorders as well as current and future possibilities for precision therapy in
neurology.

Next-Generation Sequencing Technologies

Whole exome sequencing (WES)

This technique aims to sequence the protein coding region of the genome
accounting for about 2% of the genome. As WES simultaneously analyzes almost
20,000 genes, it could be used to confirm various disorders with a single test
(Veeravigrom et al., 2015; Panmontha et al., 2016; Chongsrisawat et al., 2018;
Wright et al., 2018). All neurological phenotypes, including epilepsies, intellectual
disabilities, neuromuscular disorders, hereditary ataxias and neurodegenerative
disorders, are genetically heterogeneous. WES has become the test of choice for
molecular diagnosis of these disorders. Conventional genetic testing such as
chromosome analysis and chromosomal microarray is sometimes used in
conjunction with WES to detect chromosomal aberrations and copy number
variations, respectively. The diagnostic yield of WES in these disorders ranges

from about 30–60% (Rexach et al., 2019). The yields are higher for phenotypes with
strong genetic contributions such as infantile-onset epilepsy and severe congenital
myopathy (Ellis et al., 2020; Pergande et al., 2020).
WES in the proband and both parents or trio WES analysis can improve
the diagnostic yield. The analysis of family members can give information about
the segregation of the causative variant and a specific phenotype. The trio WES

analysis has uncovered the contribution of de novo mutations to various disorders,

78 Precision Medicine in Hereditary Neurological Disorders:
From Diagnosis to Treatment

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