Clinical and Electrophysiological Features in CMT with Mutations in NEFL Gene

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Arch Neurol. 2007 Jul;64(7):966-70.

Clinical and Electrophysiological Features in Charcot-Marie-Tooth

Disease With Mutations in the NEFL Gene.

Miltenberger-Miltenyi G, Janecke AR, Wanschitz JV, Timmerman V,

Windpassinger C, Auer-Grumbach M, Löscher WN.

Clinical Department of Neurology, Innsbruck Medical University,

Anichstrasse 35, A-6020 Innsbruck, Austria.

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 beta-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.