{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:05:13Z","timestamp":1790687113374,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,7,22]],"date-time":"2016-07-22T00:00:00Z","timestamp":1469145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>The term hereditary spastic paraplegia (<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>) covers a spectrum of genetically heterogeneous disorders in which lower limb spasticity is the common clinical feature. Many patients with childhood\u2010onset <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content> are mistakenly diagnosed with cerebral palsy (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A group of as yet molecularly undiagnosed <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content> patients were analyzed using SpastoPlex<jats:italic>,<\/jats:italic> a customized target re\u2010sequencing panel able to investigate the coding regions of 72 genes linked to <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>, spastic ataxias or related motor diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our investigations identified loss\u2010of\u2010function mutations in <jats:italic><jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>4S1<\/jats:italic>\/<jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>52 in four children (three families) who had previously received a diagnosis of diplegic\/quadriplegic <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>. The patients presented spastic paraparesis, mild facial dysmorphisms, moderate\u2010to\u2010severe intellectual disability and severe speech delay. Two patients manifested febrile seizures and childhood\u2010onset focal seizures. In all the patients, brain magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) showed a peculiar hypoplastic posterior corpus callosum, often associated with ventriculomegaly, white matter loss and cerebral atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Adaptor protein 4 (AP\u20104) deficiency disorders should be suspected in children with spastic paraparesis, cognitive deficit and absent speech accompanied by suggestive <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> features. Seizures might be amongst the clinical manifestations of the syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13085","type":"journal-article","created":{"date-parts":[[2016,7,22]],"date-time":"2016-07-22T06:23:50Z","timestamp":1469168630000},"page":"1580-1587","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Identification of mutations in <i>AP4S1\/<\/i>SPG52 through next generation sequencing in three families"],"prefix":"10.1111","volume":"23","author":[{"given":"A.","family":"Tessa","sequence":"first","affiliation":[{"name":"Molecular Medicine and Neurogenetics IRCCS Stella Maris Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Battini","sequence":"additional","affiliation":[{"name":"Child Neurology IRCCS Stella Maris Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rubegni","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Neurogenetics IRCCS Stella Maris Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Storti","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Neurogenetics IRCCS Stella Maris Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Marini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Children's Hospital \u2018A. 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