new Mylein Protein Zero gene research

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Arch Neurol. 2006 Dec;63(12):1787-94.

Effect of an R69C Mutation in the Myelin Protein Zero Gene on

Myelination and Ion Channel Subtypes.

Bai Y, Ianokova E, Pu Q, Ghandour K, Levinson R, JJ,

Ceuterick-de Groote C, Mazanec R, Seeman P, Shy ME, Li J.

Author Affiliations: Department of Neurology, Wayne State University

School of Medicine, Detroit, Mich.

BACKGROUND: Most mutations in the myelin protein zero gene (MPZ)

typically cause a severe demyelinating/dysmyelinating neuropathy

that begins in infancy or an adult-onset axonal neuropathy. Axonal

degeneration in the late-onset H10P mutation may be caused by the

disruption of axoglial interaction.

OBJECTIVE: To evaluate sural nerve biopsy samples from a patient

with early-onset Charcot-Marie-Tooth disease type 1B caused by an

arg69-to-cys (R69C) mutation.

Design and PARTICIPANTS: Biopsies of sural nerves were performed 20

years apart in a patient with an R69C mutation (early onset). In

addition, peripheral nerves were obtained from autopsy material from

a patient with a T95M mutation (late onset). These nerves were

analyzed using light microscopy of semithin sections, teased nerve

fiber immunohistochemical analysis, electron microscopy, and

immunologic electron microscopy.

MAIN OUTCOME MEASURES: Pathological changes in sural nerve.

RESULTS: Both R69C biopsy samples showed prominent demyelination and

onion bulb formation, unlike the late-onset T95M mutation, which

showed primarily axonal degeneration with no onion bulbs. The sural

biopsy sample obtained 20 years earlier from the R69C patient showed

minimal difference from the present sample, consistent with the lack

of clinical progression during the 2 decades. Teased fiber

immunohistochemical analysis of R69C revealed voltage-gated sodium

channel subtype 1.8 expressions at the nodes of Ranvier around the

areas of segmental demyelination. Internodal length in all R69C

nerve fibers was invariably short (>94% of all internodes are <150

mum).

CONCLUSIONS: Morphologic abnormalities in this early-onset R69C

neuropathy were severe in childhood but progressed very slowly after

adolescence. The switch to voltage-gated sodium channel subtype 1.8

expression at the nodes may provide clues into the pathogenesis of

this case of early-onset neuropathy, and the short internodes may

contribute to the extremely slowed conduction velocities in this

case (<10 m/s).