{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:01:57Z","timestamp":1790146917558,"version":"4.0.1"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,5,27]],"date-time":"2013-05-27T00:00:00Z","timestamp":1369612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,3]]},"abstract":"Proteolipid protein 1 (PLP1<\/jats:styled-content><\/jats:italic>) gene\u2010related disorders due to mutations in the PLP1<\/jats:styled-content><\/jats:italic> include a wide spectrum of X\u2010linked disorders ranging from severe connatal Pelizaeus\u2013Merzbacher disease (PMD<\/jats:styled-content>) to spastic paraplegia 2 (SPG2<\/jats:styled-content>). Duplications, deletions or point mutations in coding and noncoding regions of the PLP1<\/jats:styled-content><\/jats:italic> gene may occur. We report the clinical, neuroradiologic and molecular findings in six patients from two unrelated families. The affected males showed severe mental retardation, spastic tetraparesis, inability of walking and pes cavus at onset in early infancy. Brain magnetic resonance imaging (MRI<\/jats:styled-content>) showed hypomyelination and brain atrophy. Nystagmus was never observed. The affected females showed adult\u2010onset progressive spastic paraparesis leading to wheel\u2010chair dependency and subtle white matter changes on brain MRI<\/jats:styled-content>. Molecular studies in the two families identified two different intronic mutations, the novel c.622+2T<\/jats:styled-content>>C and the known c.622+1G<\/jats:styled-content>>A, leading to the skipping of PLP1<\/jats:styled-content><\/jats:italic>\u2010exon 4. The clinical presentation of the affected males did not consistently fit in any of the PLP1<\/jats:styled-content><\/jats:italic>\u2010related disorder subtypes (i.e., connatal or classic PMD<\/jats:styled-content>, SPG2<\/jats:styled-content> and \u2018PLP1<\/jats:styled-content><\/jats:italic> null syndrome\u2019), and in addition, the carrier females were symptomatic despite the severe clinical picture of their respective probands. This study provides new insight into the genotype\u2013phenotype correlations of patients with PLP1<\/jats:styled-content><\/jats:italic> splice\u2010site mutations.<\/jats:p>","DOI":"10.1111\/cge.12154","type":"journal-article","created":{"date-parts":[[2013,5,28]],"date-time":"2013-05-28T05:08:00Z","timestamp":1369717680000},"page":"267-272","source":"Crossref","is-referenced-by-count":7,"title":["Further genotype\u2013phenotype correlation emerging from two families with PLP1<\/scp><\/i> exon 4 skipping"],"prefix":"10.1111","volume":"85","author":[{"given":"Roberta","family":"Biancheri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Grossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Regis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Rossi","sequence":"additional","affiliation":[{"name":"Pediatric Neuroradiology Unit Istituto G. Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Corsolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Paola","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Cavalli","sequence":"additional","affiliation":[{"name":"Servizio di Genetica Istituti Ospedalieri di Cremona Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariasavina","family":"Severino","sequence":"additional","affiliation":[{"name":"Pediatric Neuroradiology Unit Istituto G. Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirella","family":"Filocamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,27]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"5789","volume-title":"The metabolic and molecular basis of inherited diseases","author":"Hudson LD","year":"2001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399408000677"},{"key":"e_1_2_7_4_1","unstructured":"Garbern JY Hobson GH (Updated [March 16 2010]).PLP1\u2010related disorders. In: GeneReviews at GeneTests: medical genetics information resource (database online). Seattle: University of Washington 1993\u20101999 fromhttp:\/\/www.genetests.org"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.16.5665"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-40"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1322"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2097-11.2011"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)01045-0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2273"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10762"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.01.042"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10561"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-006-9122-y"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33305"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000223551.95862.c3"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10036"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12154","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.12154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T11:39:12Z","timestamp":1694432352000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,27]]},"references-count":16,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1111\/cge.12154"],"URL":"https:\/\/doi.org\/10.1111\/cge.12154","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,27]]}}}