Shortened Internodes in CMT 1A

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Shortened Internodes in CMT 1A

ANN Poster Session Seattle Wednesday, April 29, 2009 4:00 PM

[s37.002] Characterization of Dermal Myelinated Nerve Fibers in Patients with

CMT1A

A. Saporta, Istvan K. Katona, E. Shy, Jun Li, Detroit, MI

OBJECTIVE: To investigate myelination and molecular architecture of myelinated

fibers in patients with CMT1A using glabrous skin biopsies.

BACKGROUND: CMT1A is the most common form of inherited neuropathy. It is caused

by a duplication of chromosome 17p11.2 containing the PMP22 gene, leading to its

overexpression in myelinating Schwann cells. How the gain-of-function of

over-expressed PMP22 might affect myelinating Schwann cells has not been

systematically examined in humans.

DESIGN/METHODS: Glabrous skin biopsies were collected from 12 patients with

CMT1A, 5 patients with axonal forms of CMT (CMT2) and 12 healthy controls. The

skin sections were immunostained with antibodies against PGP9.5, an axonal

marker, myelin basic protein to reveal compact myelin, and Caspr, a paranodal

marker. Slides were then examined under a confocal microscope.

RESULTS: A total of 354 internodes were identified (176 in controls, 109 in

CMT1A and 69 in CMT2). Internodal length in controls was significantly shorter

than that normally obtained in human sural nerve fibers, similar to previously

published data. There was a significant difference in internodal lengths between

CMT1A patients (74.3 27.4 m) and both controls (94.5 28.6 m) and CMT2 patients

(92.0 29.1 m) (p<0.0001, one-way ANOVA). Kruskal-Wallis analysis confirmed an

internodal length distribution in CMT1A samples that is distinctive from that in

controls and CMT2 patients ( 2 =34.7, p<0.0001). Caspr staining was

symmetrically present at most paranodes of CMT1A patients as well as controls,

suggesting that there had not been marked demyelination / remyelination in these

fibers.

CONCLUSIONS/RELEVANCE: Our results suggest that internodes are shortened in

myelinated dermal nerves of CMT1A patients and this is not likely to be the

result of extensive demyelination/remyelination. Identification of pathogenic

mechanisms in CMT has been limited by difficulties in obtaining nerve samples

from patients. The present study has expanded the use of this minimally invasive

skin biopsy technique to characterize molecular architecture in nerve fibers of

patients with CMT. Supported by: Muscular Dystrophy Association and NINDS.