{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:36:51Z","timestamp":1791329811527,"version":"4.3.1"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2001,11,1]],"date-time":"2001-11-01T00:00:00Z","timestamp":1004572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2001,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A submicroscopic duplication that contains the entire proteolipid protein gene is the major cause of Pelizaeus\u2010Merzbacher disease, an X\u2010linked central nervous system dysmyelinating disorder. Previous studies have demonstrated that carrier females for the duplication are usually asymptomatic. We describe 2 unrelated female patients who present with mild Pelizaeus\u2010Merzbacher disease or spastic paraplegia. In 1 patient, clinical features as well as cranial magnetic resonance imaging and brainstem auditory evoked potential results have improved dramatically over a 10\u2010year period. The other patient, who presented with spastic diplegia and was initially diagnosed with cerebral palsy, has also shown clinical improvement. Interphase fluorescent in situ hybridization identified a proteolipid protein gene duplication in both patients. Interphase fluorescent in situ hybridization analyses of the family members indicated that the duplication in both patients occurred as de novo events. Neither skewing of X inactivation in the peripheral lymphocytes nor proteolipid protein gene coding alterations were identified in either patient. These findings indicate that, occasionally, females with a proteolipid protein gene duplication can manifest an early\u2010onset neurological phenotype. We hypothesize that the remarkable clinical improvement is a result of myelin compensation by oligodendrocytes expressing one copy of proteolipid protein gene secondary to selection for a favorable X inactivation pattern. These findings indicate plasticity of oligodendrocytes in the formation of central nervous system myelin and suggest a potential role for stem cell transplantation therapies.<\/jats:p>","DOI":"10.1002\/ana.10036","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:45:33Z","timestamp":1030319133000},"page":"747-754","source":"Crossref","is-referenced-by-count":40,"title":["Compensating for central nervous system dysmyelination: Females with a proteolipid protein gene duplication and sustained clinical improvement"],"prefix":"10.1002","volume":"50","author":[{"given":"Ken","family":"Inoue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Scaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa G.","family":"Shaffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,11,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.6.987"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.56.10.1210"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000111361"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970317)69:2<121::AID-AJMG2>3.0.CO;2-S"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80360-8"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.5.1333"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199905)45:5<680::AID-ANA23>3.0.CO;2-H"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.6.1749"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/301933"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199905)45:5<624::AID-ANA11>3.0.CO;2-1"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/302483"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/302965"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200480"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970331)69:3<325::AID-AJMG20>3.0.CO;2-S"},{"key":"e_1_2_6_16_2","first-page":"1229","article-title":"Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen\u2010receptor gene correlates with X chromosome inactivation","volume":"51","author":"Allen RC","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199901)45:1<59::AID-ART11>3.0.CO;2-3"},{"key":"e_1_2_6_18_2","first-page":"1191","volume-title":"The metabolic and molecular basis of inherited diseases","author":"Willard HF","year":"2001"},{"key":"e_1_2_6_19_2","first-page":"330","volume-title":"Diseases of the nervous system in childhood","author":"Aicardi J","year":"1992"},{"key":"e_1_2_6_20_2","first-page":"1355","article-title":"Complete deletion of the proteolipid protein gene (PLP) in a family with X\u2010linked Pelizaeus\u2010Merzbacher disease","volume":"49","author":"Raskind WH","year":"1991","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320550402"},{"key":"e_1_2_6_22_2","first-page":"5789","volume-title":"The metabolic and molecular basis of inherited diseases","author":"Hudson LD","year":"2001"},{"key":"e_1_2_6_23_2","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1523\/JNEUROSCI.06-10-02802.1986","article-title":"Expression of the jimpy gene in the spinal cords of heterozygous female mice. 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