Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy

The Journal of Molecular Diagnostics : JMD
Vincenzo LupoCarmen Espinós

Abstract

Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (<1%) were found in 12 cases. There were no candidate variants in 18 cases, and amplification failed for one sample. The DNAJB2 c.352+1G>A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and ...Continue Reading

References

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Apr 6, 2017·International Journal of Molecular Sciences·Chi-Chun HoWing-Tat Poon
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Sep 2, 2016·Current Opinion in Neurology·Alexander M RossorMary M Reilly
Dec 27, 2016·Frontiers in Molecular Biosciences·Vincenzo LupoCarmen Espinós
May 12, 2017·Annals of Clinical and Translational Neurology·Maie WalshMelbourne Genomics Health Alliance

Citations

Oct 8, 2004·Annals of Neurology·Henry HouldenMary M Reilly
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Mar 12, 2009·European Journal of Human Genetics : EJHG·Kinga Szigeti, James R Lupski
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Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsACMG Laboratory Quality Assurance Committee

Related Concepts

Study
GJB1 gene
Charcot-Marie-Tooth Disease
Tandem Repeat Sequences
Exons
Genome
Genes
Hereditary, Type VII, Motor and Sensory Neuropathy
Pathogenic Organism
Medical Genetics Specialty

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