Abstract
Next-generation sequencing (NGS) panels are used widely in clinical diagnostics to identify genetic causes of various monogenic disease groups including neurometabolic disorders and, more recently, lysosomal storage disorders (LSDs). Many new challenges have been introduced through these new technologies, both at the laboratory level and at the bioinformatics level, with consequences including new requirements for interpretation of results, and for genetic counseling. We review some recent examples of the application of NGS technologies, with purely diagnostic and with both diagnostic and research aims, for establishing a rapid genetic diagnosis in LSDs. Given that NGS can be applied in a way that takes into account the many issues raised by international consensus guidelines, it can have a significant role even early in the course of the diagnostic process, in combination with biochemical and clinical data. Besides decreasing the delay in diagnosis for many patients, a precise molecular diagnosis is extr...
Highlights
Next-generation sequencing (NGS), referred to as massively parallel sequencing, is a high-throughput DNA sequencing technology that enables the fast generation of data on thousands to millions of base pairs of DNA from an individual patient by sequencing large numbers of genes in a single reaction.[1]
Genetic analysis has not been the primary screening tool used in the diagnosis of lysosomal storage disorders (LSDs) due to the cost and time requirements of the sequential genetic tests necessary to diagnose most of the disorders.[10,12]
The advantages of applying NGS in the diagnosis of LSDs are numerous, validation of a genetic diagnosis often still needs biochemical testing to confirm the functional consequences of a sequence variant
Summary
Next-generation sequencing (NGS), referred to as massively parallel sequencing, is a high-throughput DNA sequencing technology that enables the fast generation of data on thousands to millions of base pairs of DNA from an individual patient by sequencing large numbers of genes in a single reaction.[1]. The authors conclude that they would not propose their assay as the sole diagnostic tool but as a useful adjunct to diagnosis for specialists in the clinical management of patients with LSD especially given its advantage to provide accurate information in a short time.[12] Another example for the clinical utility of gene panels in the diagnosis of LSDs is the diagnosis of late-onset Pompe disease by a NGS approach published by Levesque et al in 2016.15 The authors developed a gene panel to analyze the coding sequences and splice site junctions of the GAA gene along with 77 other genes causing muscle disorders with overlapping phenotypes. The ASAH1 gene can be added to those tested in patients with osteolysis
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