title: Charcot-Marie-Tooth disease: frequency of genetic subtypes in a German neuromuscular center population.
abstract: Charcot-Marie-Tooth (CMT) neuropathies belong to the most common neurogenetic disorders. To date, mutations in more than 40 genes are known to be able to cause CMT. This genetic heterogeneity is a challenge for genetic diagnostics. Data on frequencies of mutations in CMT genes from large patient cohorts are needed to develop strategies for efficient genetic testing. In this study we have analysed patient histories, electrophysiological and genetic testing data in our cohort of 776 patients. In electrophysiologically demyelinating CMT, PMP22 duplication was the most common genetic cause, followed by mutations in GJB1 and MPZ. In axonal CMT, GJB1 was the most commonly affected gene, followed by MFN2 and MPZ. In CMT1, the clearance rate was 66%, in CMT2 it was 35%. Overall, the genetic clearance rate in our patient cohort was 58%. We found a higher rate of genetic diagnosis in patients seen in our neuromuscular center compared to out-of-clinic patients whose DNA was tested in our laboratory. This study provides further data on frequencies of CMT genes and subtypes and points to the importance of a thorough clinical and electrophysiological work-up for the direction of genetic testing.
authors.affiliation: University of Muenster, Department of Sleep Medicine and Neuromuscular Disorders, Albert-Schweitzer Campus 1, Geb. A1, 48149 Münster, Germany. burkhard.gess@gmail.com
authors.forename: Burkhard
authors.initials: B
authors.lastname: Gess
authors.forename: Anja
authors.initials: A
authors.lastname: Schirmacher
authors.forename: Matthias
authors.initials: M
authors.lastname: Boentert
authors.forename: Peter
authors.initials: P
authors.lastname: Young
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D017630:Connexins / Q000235:genetics*; D004558:Electric Stimulation; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D005787:Gene Frequency; D005820:Genetic Testing; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D018993:Myelin P0 Protein / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics; D012189:Retrospective Studies; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D020558:GTP Phosphohydrolases; D024101:Mitochondrial Proteins; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D000097002:Gap Junction beta-1 Protein; C560547:MPZ protein, human; C073687:PMP22 protein, human; C470018:MFN2 protein, human
keywords: Charcot-Marie-Tooth; Genetics; Hereditary neuropathy; Neuromuscular; Peripheral neuropathy