{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:07:31Z","timestamp":1790687251132,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T00:00:00Z","timestamp":1511827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT098051"],"award-info":[{"award-number":["WT098051"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>The hereditary spastic paraplegias (HSPs) are a heterogeneous group of disorders characterized by degeneration of the corticospinal and spinocerebellar tracts leading to progressive spasticity. One subtype, spastic paraplegia type 47 (SPG47 or HSP\u2010<jats:italic>AP4B1<\/jats:italic>), is due to bi\u2010allelic loss\u2010of\u2010function mutations in the <jats:italic>AP4B1<\/jats:italic> gene. AP4B1 is a subunit of the adapter protein complex 4 (AP\u20104), a heterotetrameric protein complex that regulates the transport of membrane proteins. Since 2011, 11 individuals from six families with <jats:italic>AP4B1<\/jats:italic> mutations have been reported, nine of whom had homozygous mutations and were from consanguineous families. Here we report eight patients with <jats:italic>AP4B1<\/jats:italic>\u2010associated SPG47, the majority born to non\u2010consanguineous parents and carrying compound heterozygous mutations. Core clinical features in this cohort and previously published patients include neonatal hypotonia that progresses to spasticity, early onset developmental delay with prominent motor delay and severely impaired or absent speech development, episodes of stereotypic laughter, seizures including frequent febrile seizures, thinning of the corpus callosum, and delayed myelination\/white matter loss. Given that some of the features of AP\u20104 deficiency overlap with those of cerebral palsy, and the discovery of the disorder in non\u2010consanguineous populations, we believe that AP\u20104 deficiency may be more common than previously appreciated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38561","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T16:56:48Z","timestamp":1511974608000},"page":"311-318","source":"Crossref","is-referenced-by-count":59,"title":["Clinical and genetic characterization of <i>AP4B1<\/i>\u2010associated SPG47"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0026-4714","authenticated-orcid":false,"given":"Darius","family":"Ebrahimi\u2010Fakhari","sequence":"first","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"},{"name":"Division of General Pediatrics Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Center for Integrative Brain Research Seattle Children's Research Institute Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"Dies","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Diplock","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle B.","family":"Pier","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"},{"name":"Department of Neurology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor S.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Neurology Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan C.","family":"Lanpher","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hirst","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research University of Cambridge Addenbrooke's Hospital Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medicine Columbia University Medical Center New York New 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