CMT 2: Novel C59T leader peptide mutation in the MPZ gene associated with late-o

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Eur J Neurol. 2006 Oct;13(10):1149-52.

Novel C59T leader peptide mutation in the MPZ gene associated with

late-onset, axonal, sensorimotor polyneuropathy.

Finsterer J, Miltenberger G, Rauschka H, Janecke A.

Krankenanstalt Rudolfstiftung, Vienna, Austria.

The objective of this study was to report a novel exon-1 mutation in

the myelin protein zero (MPZ) gene, resulting in axonal Charcot-Marie-

Tooth neuropathy with recurrent hyper-CK-emia. In a 64-year-old woman

slowly progressive distal lower limb weakness, muscle cramps in the

lower limb muscles, and stocking-type numbness had developed from the

age of 61. Neurologic examination revealed discrete hip flexor

weakness, weakness for foot extension, diffuse wasting of the distal

lower limb muscles, reduced patella tendon reflexes, and absent

Achilles tendon reflexes. There was recurrently elevated creatine

kinase with a maximum of 607 U/l (n, <145 U/l). Stimulation of the

peroneal and tibial nerves did not evoke a muscular response.

Electromyography was neurogenic. Biopsy of the right sural nerve

showed diffuse axonal degeneration and loss of axons of all

diameters. Muscle biopsy showed increased fiber-size variability,

angulated fibers, internalized nuclei, accumulations of nuclei,

grouped atrophic muscle fibers, and fiber splitting. Molecular

genetic analysis by PCR and direct nucleotide sequencing revealed the

heterozygous C59T exon-1 MPZ gene mutation, resulting in the amino

acid exchange S20F of the MPZ signal protein domain (leader peptide).

The novel C59T mutation in the leader peptide of the MPZ gene is

pathogenic and manifests as severe, late-onset, axonal, symmetric

sensorimotor polyneuropathy (CMT2) and hyper-CK-emia.