Improving diagnostics of rare genetic diseases with NGS approaches

Mateja Vinkšel,Karin Writzl,Borut Peterlin,Aleš Maver

doi:10.1007/s12687-020-00500-5

Mateja Vinkšel, Karin Writzl + Show 2 more

Open Access

https://doi.org/10.1007/s12687-020-00500-5

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Abstract

According to a rough estimate, one in fifteen people worldwide is affected by a rare disease. Rare diseases are therefore common in clinical practice; however, timely diagnosis of rare diseases is still challenging. Introduction of novel methods based on next-generation sequencing (NGS) technology offers a successful diagnosis of genetically heterogeneous disorders, even in case of unclear clinical diagnostic hypothesis. However, the application of novel technology differs among the centres and health systems significantly. Our goal is to discuss the impact of the implementation of NGS in the diagnosis of rare diseases and present advantages along with challenges of diagnostic approach. Systematic implementation of NGS in health systems can significantly improve the access of patients with rare diseases to diagnosis and reduce the dependence of national health systems for cross-border collaboration.

Highlights

Rare diseases present an important public health burden since they affect 6–8% of the EU population
Three main sequencing approaches are used in clinical settings and indicated for the detection of rare variants in patients with a phenotype suspected to be due to a Mendelian disease; targeted sequencing panels, whole exome sequencing (WES) and whole genome sequencing (WGS)
WES and WGS have great potential in the diagnosis of rare diseases, enabling the analysis of many genes in one test, and in the same time resulting in incidental findings and variants of unknown significance (VUS)

Summary

Introduction

Rare diseases present an important public health burden since they affect 6–8% of the EU population. Three main sequencing approaches are used in clinical settings and indicated for the detection of rare variants in patients with a phenotype suspected to be due to a Mendelian disease; targeted sequencing panels, whole exome sequencing (WES) and whole genome sequencing (WGS). WES and WGS have great potential in the diagnosis of rare diseases, enabling the analysis of many genes in one test, and in the same time resulting in incidental findings and variants of unknown significance (VUS). They represent additional challenges for clinicians and patients. During the provision of diagnostic testing for rare diseases, we participated in the identification of several novel genes for human disorders (Writzl et al 2017; Maver et al 2017, 2019, 2019; Zaman et al 2018; Loges et al 2018; Tolchin et al 2020)

Discussion

Conclusion

Findings

Compliance with ethical standards