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Rheinisch-Westfälische Technische Hochschule Aachen, Diss., 2017; ; Aachen, 71 Seiten : Illustrationen, Diagramme (2017). = Rheinisch-Westfälische Technische Hochschule Aachen, Diss., 2017, This thesis deals with hereditary neuropathies and their different forms and genetic causes. The wide genetic heterogeneity is the main reason that a rational genetic diagnosis of this group of diseases proves to be difficult and time-consuming.The aim of this study was to systematically characterize the patients with Charcot-Marie-Tooth neuropathy, i.e. clinically and genetically, who were referred to the Institute of Human Genetics in Aachen for molecular genetic testing, and to compare the results to other studies.Overall 1675 patients received molecular genetic testing for hereditary neuropathies. A database was created to analyse information about the clinical phenotype, neurological findings, family history and genetic results. 1364 patients were selected for further genotype-phenotype studies, after assigning them to certain subtypes: demyelinating CMT, axonal CMT, mixed CMT, hereditary neuropathy with liability to pressure palsies (HNPP) and hereditary motor neuropathies (HMN). 1234 of them were index patients and 130 affected relatives. After electrophysiological testing 677 (54.9%) index patients were classified as demyelinating CMT, 331 (26.8%) as axonal CMT and 13 (1.1%) as mixed CMT. 192 (15.6%) index patients were tested on suspected HNPP and 21 (1.7%) on suspected HMN.In the cohort of tested patients the detection rate for demyelinating CMT was 56% (71% of AD CMT1/CMTX) and 17% for axonal CMT (24% of AD CMT2/CMTX). The motor nerve conduction velocity was consistently lower than 38 m/s in the median nerve in patients with PMP22-duplication. It was higher than 40 m/s in patients with a mutation in MFN2, 18 – 50 m/s in patients with a mutation in GJB1/Cx32 and 8 – 41 m/s in patients with a mutation in MPZ/P0. During the analysis it became apparent that patients with CMT2A showed a broad clinical variability regardless of the type or position of the mutation in MFN2. Three genetic defects accounted for 89.3% of patients with demyelinating CMT and 84.2% of patients with axonal CMT in which a genetic diagnosis could be confirmed. This proves, that a gradual algorithm is still practical in diagnosing hereditary neuropathies. De novo mutations could be found in 1.3% of PMP22-duplications, in 25% of MPZ/P0-, in 16% of MFN2- and in none of the GJB1/Cx32-mutations. This information is important for the genetic counselling of affected families. Due to the abundance of clinical-genetic data and the size of the collective these findings have significant importance for the genetic diagnosis of hereditary neuropathies., Published by Aachen