Diagnostic algorithms in Charcot-Marie-Tooth neuropathies

• Verfasst von: Rudnik-Schöneborn, Sabine [VerfasserIn]
• Verfasst von: Tölle, D. [VerfasserIn]
• Verfasst von: Senderek, J. [VerfasserIn]
• Verfasst von: Eggermann, K. [VerfasserIn]
• Verfasst von: Elbracht, M. [VerfasserIn]
• Verfasst von: Kornak, U. [VerfasserIn]
• Verfasst von: Hagen, M. von der [VerfasserIn]
• Verfasst von: Kirschner, J. [VerfasserIn]
• Verfasst von: Leube, B. [VerfasserIn]
• Verfasst von: Müller‐Felber, W. [VerfasserIn]
• Verfasst von: Schara, U. [VerfasserIn]
• Verfasst von: Au, K. von [VerfasserIn]
• Verfasst von: Wieczorek, D. [VerfasserIn]
• Verfasst von: Bußmann, Cornelia [VerfasserIn]
• Verfasst von: Zerres, K. [VerfasserIn]
• Titel: Diagnostic algorithms in Charcot-Marie-Tooth neuropathies
• Titelzusatz: experiences from a German genetic laboratory on the basis of 1206 index patients
• Verf.angabe: 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
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 10 S.
• Fussnoten: First published: 08 April 2015 ; Gesehen am 06.05.2020
• Titel Quelle: Enthalten in: Clinical genetics
• Ort Quelle: Oxford : Wiley-Blackwell, 1970
• Jahr Quelle: 2016
• Band/Heft Quelle: 89(2016), 1, Seite 34-43
• ISSN Quelle: 1399-0004
• DOI: doi:10.1111/cge.12594
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CMT disease
• Sach-SW: electrophysiological classification
• Sach-SW: genetic diagnosis
• Sach-SW: genotype-phenotype correlation
• K10plus-PPN: 1697289738

Abstract

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.