| Autor: |
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, K, Zerres |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Clinical genetics. 89(1) |
| ISSN: |
1399-0004 |
| Popis: |
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 uniformly38 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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