• Gabriel Miltenberger-Miltenyi, Andreas R Janecke, Julia V Wanschitz, Vincent Timmerman, Christian Windpassinger, Michaela Auer-Grumbach, and Wolfgang N Löscher.
• Section of Clinical Genetics, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria.
• Arch Neurol Chicago. 2007 Jul 1; 64 (7): 966-70.

BackgroundTo 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.ObjectivesTo describe the clinical features of 11 patients with CMT and NEFL mutations and to explore possible genotype-phenotype correlations.DesignStandardized 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.SettingTwo 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.ResultsA 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.ConclusionThe results argue against an obvious genotype-phenotype correlation regarding disease onset, degree of muscle weakness, and nerve conduction slowing caused by NEFL mutations.

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