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Diagnostic algorithms in Charcot-Marie-Tooth neuropathies: experiences from a German genetic laboratory on the basis of 1206 index patients

We present clinical features and genetic results of 1206 index patients and 124 affected relatives who were referred for genetic testing of Charcot-Marie-Tooth (CMT) neuropathy at the laboratory in Aachen between 2001 and 2012. Genetic detection rates were 56% in demyelinating CMT (71% of autosomal...

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Main Authors: Rudnik-Schöneborn, Sabine (Author) , Tölle, D. (Author) , Senderek, J. (Author) , Eggermann, K. (Author) , Elbracht, M. (Author) , Kornak, U. (Author) , Hagen, M. von der (Author) , Kirschner, J. (Author) , Leube, B. (Author) , Müller‐Felber, W. (Author) , Schara, U. (Author) , Au, K. von (Author) , Wieczorek, D. (Author) , Bußmann, Cornelia (Author) , Zerres, K. (Author)
Format: Article (Journal)
Language:English
Published: 2016
In: Clinical genetics
Year: 2015, Volume: 89, Issue: 1, Pages: 34-43
ISSN:1399-0004
DOI:10.1111/cge.12594
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1111/cge.12594
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12594
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Author Notes:S. Rudnik‐Schöneborn, D. Tölle, J. Senderek, K. Eggermann, M. Elbracht, U. Kornak, M. von der Hagen, J. Kirschner, B. Leube, W. Müller‐Felber, U. Schara, K. von Au, D. Wieczorek, C. Bußmann and K. Zerres
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Summary:We present clinical features and genetic results of 1206 index patients and 124 affected relatives who were referred for genetic testing of Charcot-Marie-Tooth (CMT) neuropathy at the laboratory in Aachen between 2001 and 2012. Genetic detection rates were 56% in demyelinating CMT (71% of autosomal dominant (AD) CMT1/CMTX), and 17% in axonal CMT (24% of AD CMT2/CMTX). Three genetic defects (PMP22 duplication/deletion, GJB1/Cx32 or MPZ/P0 mutation) were responsible for 89.3% of demyelinating CMT index patients in whom a genetic diagnosis was achieved, and the diagnostic yield of the three main genetic defects in axonal CMT (GJB1/Cx32, MFN2, MPZ/P0 mutations) was 84.2%. De novo mutations were detected in 1.3% of PMP22 duplication, 25% of MPZ/P0, and none in GJB1/Cx32. Motor nerve conduction velocity was uniformly <38 m/s in median or ulnar nerves in PMP22 duplication, >40 m/s in MFN2, and more variable in GJB1/Cx32, MPZ/P0 mutations. Patients with CMT2A showed a broad clinical severity regardless of the type or position of the MFN2 mutation. Out of 75 patients, 8 patients (11%) with PMP22 deletions were categorized as CMT1 or CMT2. Diagnostic algorithms are still useful for cost-efficient mutation detection and for the interpretation of large-scale genetic data made available by next generation sequencing strategies.
Item Description:First published: 08 April 2015
Gesehen am 06.05.2020
Physical Description:Online Resource
ISSN:1399-0004
DOI:10.1111/cge.12594

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