title: Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene.
abstract: BACKGROUND
  To date, 13 different neurofilament light-chain polypeptide gene (NEFL) mutations have been identified in 55 patients with Charcot-Marie-Tooth disease (CMT) from 16 families. NEFL mutations were found to be associated with axonal and demyelinating variants of CMT.
  
  
  OBJECTIVE
  To describe the clinical features of 11 patients with CMT and NEFL mutations and to explore possible genotype-phenotype correlations.
  
  
  METHODS
  Standardized neuromuscular and nerve conduction studies were performed, and the coding regions of the peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), gap junction beta-1 protein (GJB1), and NEFL genes were analyzed by direct DNA sequencing.
  
  
  METHODS
  Two university hospitals in Austria (referral centers for neuromuscular disorders). Patients Eleven patients with CMT and NEFL mutations. Main Outcome Measure We genotyped NEFL in all of the patients and healthy relatives and correlated the genotype with the phenotype.
  
  
  RESULTS
  A novel NEFL mutation (p.L93P) was detected in 1 family with 4 affected individuals exhibiting a severe CMT phenotype. Nerve conduction velocities were intermediately slowed to a range of 35 to 39 m/s. In a second family and in a sporadic patient, a p.P8R mutation was identified with intermediate and severe nerve conduction slowing.
  
  
  CONCLUSIONS
  The results argue against an obvious genotype-phenotype correlation regarding disease onset, degree of muscle weakness, and nerve conduction slowing caused by NEFL mutations.
authors.affiliation: Section of Clinical Genetics, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Miltenberger-Miltenyi
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Janecke
authors.forename: Julia V
authors.initials: JV
authors.lastname: Wanschitz
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: Christian
authors.initials: C
authors.lastname: Windpassinger
authors.forename: Michaela
authors.initials: M
authors.lastname: Auer-Grumbach
authors.forename: Wolfgang N
authors.initials: WN
authors.lastname: Löscher
mesh_terms: D000328:Adult; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D004568:Electrodiagnosis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018908:Muscle Weakness / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics; D009431:Neural Conduction / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics*; D010375:Pedigree; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D011237:Predictive Value of Tests; D017386:Sequence Homology, Amino Acid; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D005819:Genetic Markers; D009185:Myelin Proteins; D016900:Neurofilament Proteins; D000097002:Gap Junction beta-1 Protein; C044882:neurofilament protein L