{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:27:56Z","timestamp":1791275276230,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,8,27]],"date-time":"2014-08-27T00:00:00Z","timestamp":1409097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["Starting Grant 260888"],"award-info":[{"award-number":["Starting Grant 260888"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of Health","award":["Ricerca Corrente 2013"],"award-info":[{"award-number":["Ricerca Corrente 2013"]}]},{"name":"Tunisian Ministry of Health"},{"name":"Tunisian Ministry of Scientific Research"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">PLA<\/jats:styled-content>2G6<\/jats:italic> gene are causative of <jats:italic>PLA2G6<\/jats:italic>\u2010associated neurodegeneration (<jats:styled-content style=\"fixed-case\">PLAN<\/jats:styled-content>), a spectrum of neurodegenerative conditions including infantile, childhood and adult onset forms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventeen North African patients with a clinical suspicion of infantile\u2010onset <jats:styled-content style=\"fixed-case\">PLAN<\/jats:styled-content> underwent clinical, neurophysiological and neuroimaging examinations, and <jats:italic><jats:styled-content style=\"fixed-case\">PLA<\/jats:styled-content>2G6<\/jats:italic> sequencing. Haplotype analysis was performed to date the identified founder mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients carried biallelic mutations in <jats:italic><jats:styled-content style=\"fixed-case\">PLA<\/jats:styled-content>2G6<\/jats:italic>. Sixteen children had the commonest form of infantile\u2010onset <jats:styled-content style=\"fixed-case\">PLAN<\/jats:styled-content>, with early onset of psychomotor regression, hypotonia, pyramidal and cerebellar signs, and abnormal ocular movements. The phenotype was highly homogeneous, with rapid development of severe spastic tetraparesis, cognitive impairment and optic atrophy. Neuroimaging showed cerebellar atrophy and claval hypertrophy to be the commonest and earliest signs, whilst cerebellar cortex hyperintensity and pallidal iron deposition were later findings. Motor or sensory\u2010motor neuropathy and electroencephalogram fast rhythms were also frequent. Nine patients from six families shared the same founder mutation (p.V691del) which probably arose by the late seventeenth century. Only one patient fitted the diagnosis of the much rarer childhood\u2010onset <jats:styled-content style=\"fixed-case\">PLAN<\/jats:styled-content>. Despite the early onset (18\u00a0months), clinical progression was slower, with behavioral disturbances and dystonia. Typical features of infantile\u2010onset <jats:styled-content style=\"fixed-case\">PLAN<\/jats:styled-content> such as hypotonia, nystagmus\/strabismus, optic atrophy, electroencephalogram fast rhythms and motor neuropathy were absent. Cerebellar atrophy, claval hypertrophy and pallidal hypointensity were evident at brain magnetic resonance imaging. This patient carried a missense variant predicted to be less deleterious.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">PLAN<\/jats:styled-content>\u2010associated phenotypes and the challenges of diagnosing the childhood\u2010onset form are delineated, and a common North African founder mutation is identifed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.12552","type":"journal-article","created":{"date-parts":[[2014,8,27]],"date-time":"2014-08-27T13:17:52Z","timestamp":1409145472000},"page":"178-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Infantile and childhood onset <i><scp>PLA<\/scp>2G6<\/i>\u2010associated neurodegeneration in a large North African cohort"],"prefix":"10.1111","volume":"22","author":[{"given":"M.","family":"Romani","sequence":"first","affiliation":[{"name":"IRCCS Casa Sollievo della Sofferenza Mendel Laboratory San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Kraoua","sequence":"additional","affiliation":[{"name":"Research Unit 06\/11 and Department of Child and Adolescent Neurology National Institute Mongi Ben Hmida of Neurology Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Micalizzi","sequence":"additional","affiliation":[{"name":"IRCCS Casa Sollievo della Sofferenza Mendel Laboratory San Giovanni Rotondo Italy"},{"name":"Department of Medical and Surgical Pediatric Sciences University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Klaa","sequence":"additional","affiliation":[{"name":"Research Unit 06\/11 and Department of Child and Adolescent Neurology National Institute Mongi Ben Hmida of Neurology Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Benrhouma","sequence":"additional","affiliation":[{"name":"Research Unit 06\/11 and Department of Child and Adolescent Neurology National Institute Mongi Ben Hmida of Neurology Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Drissi","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology National Institute Mongi Ben Hmida of Neurology Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Turki","sequence":"additional","affiliation":[{"name":"Research Unit 06\/11 and Department of Child and Adolescent Neurology National Institute Mongi Ben Hmida of Neurology Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Castellana","sequence":"additional","affiliation":[{"name":"IRCCS Casa Sollievo della Sofferenza Mendel Laboratory San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Mazza","sequence":"additional","affiliation":[{"name":"IRCCS Casa Sollievo della Sofferenza Mendel Laboratory San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. M.","family":"Valente","sequence":"additional","affiliation":[{"name":"IRCCS Casa Sollievo della Sofferenza Mendel Laboratory San Giovanni Rotondo Italy"},{"name":"Section of Neurosciences Department of Medicine and Surgery University of Salerno Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Gouider\u2010Khouja","sequence":"additional","affiliation":[{"name":"Research Unit 06\/11 and Department of Child and Adolescent Neurology National Institute Mongi Ben Hmida of Neurology Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2011.03955.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-410502-7.00003-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012897"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.02.009"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01417.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23617"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12327"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1826"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/508572"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000327094.67726.28"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2012.03856.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2012.07.016"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.02.078"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32012"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2011.22"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076831"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.03.008"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.061929"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2008.02397.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000310986.48286.8e"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2008.01.005"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.12552","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.12552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T22:43:21Z","timestamp":1695509001000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.12552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,27]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1111\/ene.12552"],"URL":"https:\/\/doi.org\/10.1111\/ene.12552","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,27]]},"assertion":[{"value":"2014-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-07-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}