neurofilament light (NEFL) mutations research

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Abstract from Neuromuscul Disord. 2004 Feb; 14(2): 147-57.

The novel neurofilament light (NEFL) mutation Glu397Lys is associated

with a clinically and morphologically heterogeneous type of

Charcot-Marie-Tooth neuropathy.

Zuchner S, Vorgerd M, Sindern E, Schroder JM.

Institut fur Neuropathologie, Universitatsklinikum der RWTH Aachen,

Pauwelsstrasse 32, 52074, Aachen, Germany

Charcot-Marie-Tooth disease comprises a heterogeneous group of

hereditary neuropathies which fall into two main groups: demyelinating

CMT1 with reduced nerve conduction velocity and axonal CMT2 with normal

nerve conduction velocity. The neuropathological features correspond in

most cases to this classification. Four genes were recently identified

to cause autosomal dominant CMT2, including the neurofilament light

gene. Thus far, only few mutations have been reported in neurofilament

light involving eight amino acids of the gene. We identified a novel

mutation, Glu397Lys, in a conserved motive signaling the end of the rod

domain. The affected family members from three generations showed

strikingly different clinical phenotypes, including weakness of the

lower extremities, foot deformities, and deafness. The mutation was

associated with nerve conduction velocities ranging from 27 m/s in a

25-year-old female to 43 m/s in an 82-year-old male in the lower

extremity motor nerves. Sural nerve biopsies of two affected subjects

were analyzed by light and electron microscopy. The pathological changes

consisted of a reduction of predominantly large myelinated nerve fibers

and various stages of onion bulb formation as typically seen in CMT1.

This correlative study further confirms that neurofilament light gene

mutations cause a wide clinical spectrum. Thus, analysis of the

neurofilament light gene should not be restricted to pure axonal

neuropathies.