G2Cdb::Allele report

Mutation type
P

Altered genes (1)

Gene Symbol Species Description
G00001806 PLP1 Homo sapiens proteolipid protein 1

Diseases (1)

Disease Description Nervous effect
D00000155 Pelizaeus-Merzbacher disease Y

Literature (1)

Pubmed - other

  • Schwann cell expression of PLP1 but not DM20 is necessary to prevent neuropathy.

    Shy ME, Hobson G, Jain M, Boespflug-Tanguy O, Garbern J, Sperle K, Li W, Gow A, Rodriguez D, Bertini E, Mancias P, Krajewski K, Lewis R and Kamholz J

    Department of Neurology and Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.

    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.

    Funded by: NINDS NIH HHS: R01 NS043783

    Annals of neurology 2003;53;3;354-65

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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