Exome sequencing: how to understand it

A clinical diagnostic algorithm for early onset cerebellar ataxia

“…These include testing of specific gene panels (Targeted Resequencing Panels (TRS)), of coding regions (Whole Exome Sequencing (WES)) with or without a filter for specific genes and of the entire genome (Whole Genome Sequencing (WGS)). 9,10 In recent years, many laboratories apply WES as a diagnostic NGS strategy for the majority of diagnostic applications. It is important to realize that there are some limitations to these novel techniques.…”

“…Secondly, at this moment NGS does not detect repeat expansion disorders and large rearrangements (deletions and duplications). 9,92 Mutations in noncoding parts of the genome (such as deep intronic regions or promotor regions) can only be detected with WGS. Thirdly, EOAc patients may often present with a mixed phenotype, complicating the selection of the gene panel.…”

Diagnostic approach to paediatric movement disorders: a clinical practice guide

“…Whole‐exome sequencing (WES) is the most applied basic technique for NGS 30 . In general, the first step in the genetic diagnostic process of PMDs is the use of a WES with a movement‐disorder‐specific filter.…”

“…Whole-exome sequencing (WES) is the most applied basic technique for NGS. 30 In general, the first step in the genetic diagnostic process of PMDs is the use of a WES with a movement-disorder-specific filter. In these cases, a filter with predefined genes associated with the main movement disorder phenotype will be analysed.…”

“…When using NGS techniques one should be aware of the limitations: (1) the genes in the filter need to be selected carefully and be update regularly; (2) trinucleotide repeat expansion disorders, large rearrangement deletions and duplications, mutations in the non‐coding part of the genome (such as deep intronic regions or promotor regions) are not detected; 30 (3) mitochondrial diseases due to mutations in mitochondrial DNA are not detected by most laboratories using WES; one should realize that the current diagnostic yield of NGS techniques is only 15% to 40%, but probably will increase in forthcoming years.…”