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Gabriel Miltenberger-Miltenyi, MD; Andreas R. Janecke, MD; Julia V. Wanschitz, MD; Vincent Timmerman, PhD; Christian Windpassinger, PhD; Michaela Auer-Grumbach, MD, PhD; Wolfgang N. Löscher, MD, PhD

Arch Neurol. 2007;64(7):966-970.

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.

Objectives  To describe the clinical features of 11 patients with CMT and NEFL mutations and to explore possible genotype-phenotype correlations.

Design  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 β-1 protein (GJB1), and NEFL genes were analyzed by direct DNA sequencing.

Setting  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.

Conclusion  The results argue against an obvious genotype-phenotype correlation regarding disease onset, degree of muscle weakness, and nerve conduction slowing caused by NEFL mutations.

Author Affiliations: Section of Clinical Genetics (Drs Miltenberger-Miltenyi and Janecke) and Clinical Department of Neurology (Drs Wanschitz and Löscher), Innsbruck Medical University, Innsbruck, Austria; Peripheral Neuropathy Group, Molecular Genetics Department, Flanders Interuniversity Institute for Biotechnology, Institute Born Bunge, University of Antwerp, Antwerp, Belgium (Dr Timmerman); Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario (Dr Windpassinger); and Institute of Medical Biology and Human Genetics, Medical-University Graz, Graz, Austria (Drs Windpassinger and Auer-Grumbach).

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