Journal article
Schwann Cell Expression of PLP1 but Not DM20 Is Necessary to Prevent Neuropathy
Annals of neurology, Vol.53(3), pp.354-365
03/2003
DOI: 10.1002/ana.10466
PMCID: PMC4744322
PMID: 12601703
Abstract
Proteolipid protein (PLP1) and its alternatively spliced isoform, DM20, are the major myelin proteins in the CNS, but are also expressed in the PNS. The proteins have an identical sequence except for 35 amino acids in PLP1 (the PLP1-specific domain) not present in DM20. Mutations of PLP1/DM20 cause Pelizaeus-Merzbacher Disease (PMD), a leukodystrophy, and in some instances, a peripheral neuropathy. To identify which mutations cause neuropathy, we have evaluated a cohort of patients with PMD and PLP1 mutations for the presence of neuropathy. As shown previously, all patients with PLP1 null mutations had peripheral neuropathy. We also identified 4 new PLP1 point mutations that cause both PMD and peripheral neuropathy, three of which truncate PLP1 expression within the PLP1-specific domain, but do not alter DM20. The fourth, a splicing mutation, alters both PLP1 and DM20, and is probably a null mutation. Six PLP1 point mutations predicted to produce proteins with an intact PLP1-specific domain do not cause peripheral neuropathy. Sixty-one individuals with PLP1 duplications also had normal peripheral nerve function. These data demonstrate that expression of PLP1 but not DMSO is necessary to prevent neuropathy, and suggest that the 35 amino acid PLP1-specific domain plays an important role in normal peripheral nerve function.
Details
- Title: Subtitle
- Schwann Cell Expression of PLP1 but Not DM20 Is Necessary to Prevent Neuropathy
- Creators
- Michael E Shy - Department of Neurology, Wayne State University School of Medicine, Detroit, MIGrace Hobson - Nemours Biomedical Research, Nemours Children's Clinic–Wilmington, Alfred I. duPont Hospital for Children, Wilmington, DEManisha Jain - Department of Neurology, Wayne State University School of Medicine, Detroit, MIOdile Boespflug-Tanguy - INSERM UMR 384, Faculte de Medecine, Clermont-Ferrand, Paris, FranceJames Garbern - Department of Neurology, Wayne State University School of Medicine, Detroit, MIKaren Sperle - Nemours Biomedical Research, Nemours Children's Clinic–Wilmington, Alfred I. duPont Hospital for Children, Wilmington, DEWen Li - Department of Neurology, Wayne State University School of Medicine, Detroit, MIAlex Gow - Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MIDiana Rodriguez - Department of Pediatric Neurology, Saint Vincent de Paul and Trousseau Hospital, Paris, FranceEnrico Bertini - Department of Neurosciences, Division of Pediatric Neurology, Unit of Molecular Medicine, Bambino Gesu’ Hospital IRCCS, Rome, ItalyPedro Mancias - University of Texas–Houston Medical Center, Houston, TXKaren Krajewski - Department of Neurology, Wayne State University School of Medicine, Detroit, MIRichard Lewis - Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MIJohn Kamholz - Department of Neurology, Wayne State University School of Medicine, Detroit, MI
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.53(3), pp.354-365
- DOI
- 10.1002/ana.10466
- PMID
- 12601703
- PMCID
- PMC4744322
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Language
- English
- Date published
- 03/2003
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984016078202771
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