CMT 1A: PMP22 Expression in Dermal Nerve Compact Myelin Does Not Correlate

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PMP22 Expression in Dermal Nerve Compact Myelin Does Not Correlate

with Disability in Patients with CMT1A

Istvan Katona, Xingyao Wu, Francies, Carly Siskind, a

Feely, Shy, Jun Li, Detroit, MI

OBJECTIVE: To identify correlations between patient impairment and

PMP22 protein and mRNA levels in Charcot Marie Tooth disease 1A

(CMT1A).

BACKGROUND: CMT1A, the most common form of CMT, is caused by a 1.4 Mb

duplication on chromosome 17p11.2, which contains the PMP22 gene.

Increased expression of PMP22 protein in compact myelin of peripheral

nerves has been demonstrated by sural nerve and skin biopsies. In

contrast, decreased PMP22 expression has been found in biopsies of

patients with hereditary neuropathy with liability to pressure

palsies (HNPP), a distinct phenotype caused by a deletion of the same

1.4 Mb sequence. It is therefore thought that differences in PMP22

protein levels cause the distinct CMT1A and HNPP phenotypes. We have

observed variable PMP22 levels of over-expression in skin biopsies of

patients with CMT1A. We hypothesized that these varying levels of

PMP22 expression may determine the variable disabilities of CMT1A

patients.

DESIGN/METHODS: PMP22 expression in dermal nerves was measured by

taking skin biopsies from patients with CMT1A (n=20) and healthy

controls (n=7). Immunological electron microscopy (immunoEM) with

antibodies against PMP22 was performed on the skin biopsies to

quantify PMP22 expression. Similar biopsies were performed for Real

Time PCR to measure PMP22 mRNA levels. Results were correlated with

disabilities, as measured by the validated CMT Neuropathy Score

(CMTNS).

RESULTS: Results demonstrated that most, but not all CMT1A patients,

had elevated PMP22 levels in myelin compared to controls, consistent

with our previous observations in a smaller series. However, there

was no correlation between disabilities and the level of over-

expression. mRNA studies are ongoing.

CONCLUSIONS/RELEVANCE: These data suggest that variable levels of

PMP22 in myelin do not explain phenotypic variability of CMT1A.

Whether PMP22 protein or mRNA levels will be useful for natural

history studies or clinical trials will require longitudinal studies

with these techniques.