Abstract
Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of hereditary polyneuropathies. Variants in more than 80 different genes have been associated with the disorder. In recent years, the introduction of next generation sequencing (NGS) techniques have completely changed the genetic diagnostic approach from the analysis of a handful of genes to the analysis of all genes associated with CMT in a single run. In this study we describe the CMT diagnostics in Denmark in 1992–2012, prior to the implementation of NGS, by combining laboratory- and national registry data. We investigate the effect of implementing a targeted NGS approach of 63 genes associated with CMT in the diagnostic laboratory setting. This was performed by analyzing a cohort of 195 samples from patients previously analyzed by Sanger sequencing and quantitative analysis for the common causes of CMT without reaching a molecular diagnosis. A total of 1442 CMT analyses were performed in Denmark in the period 1992–2012; a disease-causing variant was detected in 21.6% of the cases. Interestingly, the diagnosis was genetically confirmed in significantly more women than men; 25.9% compared to18.5%. In our study cohort, we found a 5.6% increase in the diagnostic yield with the introduction of a targeted NGS approach.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Medical Genetics |
| Vol/bind | 62 |
| Udgave nummer | 1 |
| Sider (fra-til) | 1-8 |
| ISSN | 1769-7212 |
| DOI | |
| Status | Udgivet - jan. 2019 |
Finansiering
We are grateful to the following for assistance in medical records retrieval: Dea Svaneby, Dept. of Clinical Genetics, Vejle, Suzanne Lindquist, Dept. of Clinical Genetics, Rigshospitalet, Lisbeth Landschoff, Dept. of Neurology, Glostrup, Lise Korbo, Dept. of Neurology, Bispebjerg, Birgitte Forsom Sandal, Dept. of Neurology, Holstebro, and the administrative staff at the Departments of Neurology in Roskilde and Hillerød and the Departments of Pediatrics in Næstved and Hvidovre. From the Dept. of Clinical Genetics, Aarhus, we wish to thank Jan Hansen and Inger Junker for the retrieval of genetic analysis data, and Klaus Riege Cookiemayn Nielsen and Christina Strande Sønderskov for the preparation of DNA and Sanger sequencing of samples. We also wish to thank Michael Væth from The Department of Public Health, Section for Biostatistics at Aarhus University for technical assistance in the management of register data. This work has been supported by a grant from Innovation Fund Denmark ( 037-2010-1 ), Aarhus University Hospital and Aarhus University , and was also funded by Fonden til Lægevidenskabens Fremme , Vanførefonden , Torben og Alice Frimodts Fond , Aase og Einar Danielsens Fond , Civilingeniør Frode V . Nyegaard og hustrus Fond and Familien Hede Nielsens Fond . Appendix A