{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:26:53Z","timestamp":1778732813551,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":2747,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1997,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Charcot\u2010Marie\u2010Tooth type 1B is an uncommon form of hereditary motor and sensory neuropathy caused by mutations in the P<jats:sub>o<\/jats:sub> myelin protein gene on chromosome 1. We report here a 20\u2010year observation of 13 members of the first family with Charcot\u2010Marie\u2010Tooth disease to demonstrate linkage to chromosome 1 and now known to have a C270A mutation in the P<jats:sub>o<\/jats:sub> gene altering the extracellular domain of the protein. Affected individuals generally show an early age at onset, often indicated by delayed ability to walk. Proximal muscle weakness of the lower extremities is common and often marked, but the individuals remain ambulatory and there is no decrease in life span. Motor nerve conduction velocities of the fastest fibers are severely slowed (mean, 9\u201311 m\/sec), even when compared with 3 families having Charcot\u2010Marie Tooth type 1A (mean, 19\u201321 m\/sec). Variability of disability between family members suggests that genetic and environmental factors in addition to the P<jats:sub>o<\/jats:sub> mutation play a role in the final phenotype. Nerve biopsy specimens demonstrate hypertrophy, onion bulb formation, loss of myelinated fibers, and occasional myelin thickening similar to that described in P<jats:sub>o<\/jats:sub> myelin knockout mice. Autopsy of the 92\u2010year\u2010old great\u2010grandmother in this family demonstrated diffuse involvement of sensory and motor nerves, with loss of myelin in the posterior columns of the spinal cord and loss of anterior horn neurons but without other involvement of the central nervous system. This family demonstrates the long\u2010term phenotypic consequences on the peripheral nervous system system of a specific point mutation in the P<jats:sub>o<\/jats:sub> myelin gene.<\/jats:p>","DOI":"10.1002\/ana.410410409","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T14:58:49Z","timestamp":1104591529000},"page":"463-469","source":"Crossref","is-referenced-by-count":53,"title":["Clinical and pathological phenotype of the original family with Charcot\u2010Marie\u2010Tooth type 1B: A 20\u2010year study"],"prefix":"10.1002","volume":"41","author":[{"given":"Thomas D.","family":"Bird","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George H.","family":"Kraft","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hillary P.","family":"Lipe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimbra L.","family":"Kenney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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