Gene dosage effects in hereditary peripheral neuropathy: Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies

Jean Marc Gabriel, Beat Erne, Davide Pareyson, Angelo Sghirlanzoni, Franco Taroni, Andreas J. Steck

Research output: Contribution to journalArticle

Abstract

A duplication of a 1.5-Megabase genomic region encompassing the gene for the peripheral myelin protein 22 (PMP22) is found on chromosome 17p11.2-12 in Charcot-Marie-Tooth disease type 1A (CMT1A), whereas the reciprocal deletion is associated with hereditary neuropathy with liability to pressure palsies (HNPP). Since most CMT1A patients harbor three copies of the PMP22 gene, and most HNPP patients carry only a single copy, a gene dosage effect has been proposed as a mechanism for both diseases. We have analyzed the steady-state expression of PMP22 protein in sural nerve biopsies from three CMT1A and four HNPP patients. Quantitative immunohistochemical determination showed that PMP22 protein expression relative to that of myelin protein zero and myelin basic protein was increased in all CMT1A patients and reduced in all HNPP patients, as compared with biopsy samples of patients with normal PMP22 gene expression. These data demonstrate that both neuropathies result from an imbalance of PMP22 protein expression.

Original languageEnglish
Pages (from-to)1635-1640
Number of pages6
JournalNeurology
Volume49
Issue number6
Publication statusPublished - Dec 1997

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Myelin Proteins
Charcot-Marie-Tooth Disease
Gene Dosage
Peripheral Nervous System Diseases
Biopsy
Myelin P0 Protein
Chromosomes, Human, Pair 12
Sural Nerve
Proteins
Myelin Basic Protein
Genes
Tomaculous neuropathy
Gene Expression

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Gene dosage effects in hereditary peripheral neuropathy: Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies",
abstract = "A duplication of a 1.5-Megabase genomic region encompassing the gene for the peripheral myelin protein 22 (PMP22) is found on chromosome 17p11.2-12 in Charcot-Marie-Tooth disease type 1A (CMT1A), whereas the reciprocal deletion is associated with hereditary neuropathy with liability to pressure palsies (HNPP). Since most CMT1A patients harbor three copies of the PMP22 gene, and most HNPP patients carry only a single copy, a gene dosage effect has been proposed as a mechanism for both diseases. We have analyzed the steady-state expression of PMP22 protein in sural nerve biopsies from three CMT1A and four HNPP patients. Quantitative immunohistochemical determination showed that PMP22 protein expression relative to that of myelin protein zero and myelin basic protein was increased in all CMT1A patients and reduced in all HNPP patients, as compared with biopsy samples of patients with normal PMP22 gene expression. These data demonstrate that both neuropathies result from an imbalance of PMP22 protein expression.",
author = "Gabriel, {Jean Marc} and Beat Erne and Davide Pareyson and Angelo Sghirlanzoni and Franco Taroni and Steck, {Andreas J.}",
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T2 - Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies

AU - Gabriel, Jean Marc

AU - Erne, Beat

AU - Pareyson, Davide

AU - Sghirlanzoni, Angelo

AU - Taroni, Franco

AU - Steck, Andreas J.

PY - 1997/12

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N2 - A duplication of a 1.5-Megabase genomic region encompassing the gene for the peripheral myelin protein 22 (PMP22) is found on chromosome 17p11.2-12 in Charcot-Marie-Tooth disease type 1A (CMT1A), whereas the reciprocal deletion is associated with hereditary neuropathy with liability to pressure palsies (HNPP). Since most CMT1A patients harbor three copies of the PMP22 gene, and most HNPP patients carry only a single copy, a gene dosage effect has been proposed as a mechanism for both diseases. We have analyzed the steady-state expression of PMP22 protein in sural nerve biopsies from three CMT1A and four HNPP patients. Quantitative immunohistochemical determination showed that PMP22 protein expression relative to that of myelin protein zero and myelin basic protein was increased in all CMT1A patients and reduced in all HNPP patients, as compared with biopsy samples of patients with normal PMP22 gene expression. These data demonstrate that both neuropathies result from an imbalance of PMP22 protein expression.

AB - A duplication of a 1.5-Megabase genomic region encompassing the gene for the peripheral myelin protein 22 (PMP22) is found on chromosome 17p11.2-12 in Charcot-Marie-Tooth disease type 1A (CMT1A), whereas the reciprocal deletion is associated with hereditary neuropathy with liability to pressure palsies (HNPP). Since most CMT1A patients harbor three copies of the PMP22 gene, and most HNPP patients carry only a single copy, a gene dosage effect has been proposed as a mechanism for both diseases. We have analyzed the steady-state expression of PMP22 protein in sural nerve biopsies from three CMT1A and four HNPP patients. Quantitative immunohistochemical determination showed that PMP22 protein expression relative to that of myelin protein zero and myelin basic protein was increased in all CMT1A patients and reduced in all HNPP patients, as compared with biopsy samples of patients with normal PMP22 gene expression. These data demonstrate that both neuropathies result from an imbalance of PMP22 protein expression.

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