{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T17:44:13Z","timestamp":1758476653647},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,4,18]],"date-time":"2012-04-18T00:00:00Z","timestamp":1334707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Pelizaeus\u2010Merzbacher disease (PMD) is a recessive, X\u2010linked leukoencephalopathy attributed to impaired myelination during central nervous system development, caused by defects in the proteolipid protein 1 (<jats:italic>PLP1<\/jats:italic>) gene. PMD presents clinical variability, ranging from the severe connatal form to the classic form.<\/jats:p><\/jats:sec><jats:sec><jats:title>CASES<\/jats:title><jats:p>We report the clinical and molecular findings of two affected males, three carrier females, and an aborted male fetus with familial PMD. The two male probands presented with severe PMD phenotype and intellectual disability. High\u2010resolution oligonucleotide\u2010based array comparative genomic hybridization (aCGH) identified an Xq22.2 duplication of 320.6 kb (102641391\u2010102961998, hg18), including the <jats:italic>PLP1<\/jats:italic> gene and surrounding chromosomal region. Postmortem examination of the aborted fetus at 25 weeks' gestation showed focal subcortical white matter degeneration, focal gliosis, and cerebellar atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Genotype\u2010phenotype correlation is provided. In the connatal form of PMD, leukodystrophy and cerebellar atrophy can occur antenatally and be established at 25 weeks' gestation. The observation of degenerative brain lesions occurring before the onset of subcortical myelination suggests that the <jats:italic>PLP1<\/jats:italic> gene has a more complex role in human brain development, exceeding its structural function in myelin formation. Birth Defects Research (Part A), 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23015","type":"journal-article","created":{"date-parts":[[2012,4,18]],"date-time":"2012-04-18T09:09:58Z","timestamp":1334740198000},"page":"494-498","source":"Crossref","is-referenced-by-count":2,"title":["Familial Pelizaeus\u2013Merzbacher disease caused by a 320.6\u2010kb Xq22.2 duplication and the pathological findings of a male fetus"],"prefix":"10.1002","volume":"94","author":[{"given":"Sophia","family":"Kitsiou\u2010Tzeli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Konstantinidou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christalena","family":"Sofocleous","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantina","family":"Kosma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Areti","family":"Syrmou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krinio","family":"Giannikou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavros","family":"Sifakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Periklis","family":"Makrythanasis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Tzetis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,4,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2001.tb00383.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6182-8"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-40"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(12)80271-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970905)71:4<475::AID-AJMG20>3.0.CO;2-C"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-004-0207-y"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000111420"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33447"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20732"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3843(14)60142-0"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00290964"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.07.007"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/1817-1745.76122"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.04.002"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2009.02.011"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10660"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0562-8"},{"key":"e_1_2_6_19_1","first-page":"1822","article-title":"MR revealed myelination in the cerebral corticospinal tract as a marker for Pelizaeus\u2010Merzbachte\u0155s disease with proteolipid protein gene duplication","volume":"20","author":"Takanashi J","year":"1999","journal-title":"Am J Neuroradiol"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3309-z"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399408000677"}],"container-title":["Birth Defects Research Part A: Clinical and Molecular Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdra.23015","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T07:54:51Z","timestamp":1697615691000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.23015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,18]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,6]]}},"alternative-id":["10.1002\/bdra.23015"],"URL":"https:\/\/doi.org\/10.1002\/bdra.23015","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4,18]]}}}