Inherited peripheral neuropathies (IPN) represent a large heterogenous group of hereditary diseases with more than 100 causative genes reported to date. In this context, targeted next-generation sequencing (NGS) offers the opportunity to screen all these genes with high efficiency in order to unravel the genetic basis of the disease. Here, the authors compared the diagnostic yield of targeted NGS with their previous gene by gene Sanger sequencing strategy by comparing the results of NGS in a cohort of 123 patients and the results of Sanger sequencing in a group of 56 patients. They compared the molecular diagnostic resolution rates between demyelinating and axonal CMT forms. They also report on new likely pathogenic variants, not yet described in the literature, and present the most frequently mutated genes. They also describe two candidate copy number variations (CNVs), identified from the NGS data. NGS allowed to identify causal mutations in a shorter and cost-effective time. However, NGS leads to the identification of numerous variants of unknown significance, which interpretation requires interdisciplinary collaborations between molecular geneticists, clinicians and (neuro)pathologists.
>Read full text: Bacquet J, Stojkovic T, Boyer A, et al. Molecular diagnosis of inherited peripheral neuropathies by targeted next-generation sequencing: molecular spectrum delineation. BMJ Open. 2018 Oct 28;8(10):e021632.