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Peripheral Neuropathy Caused by Proteolipid Protein Gene Mutations
Author(s) -
GARBERN JAMES Y.,
CAMBI FRANCA,
LEWIS RICHARD,
SHY MICHAEL,
SIMA ANDERS,
KRAFT GEORGE,
VALLAT J. M.,
BOSCH E. P.,
HODES M. E.,
DLOUHY STEPHEN,
RASKIND WENDY,
BIRD THOMAS,
MACKLIN WENDY,
KAMHOLZ JOHN
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08597.x
Subject(s) - proteolipid protein 1 , missense mutation , peripheral nervous system , nonsense mutation , gene , peripheral neuropathy , mutation , myelin , gene product , null allele , genetics , biology , central nervous system , allele , gene expression , endocrinology , myelin basic protein , diabetes mellitus
Pelizaeus‐Merzbacher disease (PMD) is a dysmyelinating disorder of the central nervous system typically caused by duplications or missense mutations of the proteolipid protein (PLP) gene. Most investigators have found that peripheral nerve function and structure is normal in PMD patients. We have found that null mutations of the PLP gene cause demyelinating peripheral neuropathy, whereas duplications and a proline 14 to leucine mutation do not affect nerve function. A family with a nonsense mutation at position 144, which affects only PLP but not the alternatively spliced gene product DM20, has a very mild syndrome, including normal peripheral nerve function. Our findings suggest that DM20 alone is sufficient to maintain normal nerve function and that there may be domains of PLP/DM20 that have a relatively more active role in the peripheral nervous system compared with that in the central nervous system.