{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:23:53Z","timestamp":1784697833016,"version":"3.55.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"CureSPG47 Inc., the Spastic Paraplegia Foundation (SPF) Inc.,"},{"name":"Thrasher Foundation"},{"name":"Lovejoy Award"},{"name":"University of W\u00fcrzburg Graduate School of Life Sciences Scholarship"},{"name":"University of Siena \u201cPegaso Scholarship\u201d"},{"name":"Burroughs Wellcome Career Award for Medical Scientists","award":["1805016N"],"award-info":[{"award-number":["1805016N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0\u201349.3 years). While the mean age at symptom onset was 0.8 \u00b1 0.6 years [standard deviation (SD), range 0.2\u20135.0], the mean age at diagnosis was 10.2 \u00b1 8.5 years (SD, range 0.1\u201346.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 \u00b1 5.1 years, SD) and later tetraplegia (mean age: 16.1 \u00b1 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 \u00b1 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 \u00b1 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an \u2018AP-4 deficiency syndrome\u2019. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.<\/jats:p>","DOI":"10.1093\/brain\/awz307","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T19:32:18Z","timestamp":1568316738000},"source":"Crossref","is-referenced-by-count":21,"title":["Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0026-4714","authenticated-orcid":false,"given":"Darius","family":"Ebrahimi-Fakhari","sequence":"first","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Teinert","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Division of Child Neurology and Metabolic Medicine, Centre for Paediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Behne","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Wimmer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"D'Amore","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Molecular Medicine, IRCCS Fondazione Stella Maris, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Eberhardt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Brechmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana M","family":"Jensen","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Premsai","family":"Nagabhyrava","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Geisel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Carmody","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzma","family":"Shamshad","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira A","family":"Dies","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Yuskaitis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L","family":"Salussolia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ebrahimi-Fakhari","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Saarland University Medical Center, Homburg\/Saar, Germany"},{"name":"Department of General Pediatrics, University Children's Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni S","family":"Pearson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-7519","authenticated-orcid":false,"given":"Afshin","family":"Saffari","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine, Centre for Paediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine, Centre for Paediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine, Centre for Paediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Volkmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Wiesener","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Friedrich-Alexander Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Bearden","sequence":"additional","affiliation":[{"name":"Child Neurology, University of Rochester School of Medicine, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenela","family":"Lakhani","sequence":"additional","affiliation":[{"name":"Center for Neurogenetics, Weill Cornell Medical College, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devorah","family":"Segal","sequence":"additional","affiliation":[{"name":"Center for Neurogenetics, Weill Cornell Medical College, New York, NY, USA"},{"name":"Division of Child Neurology, Weill Cornell Medicine, New York City, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anaita","family":"Udwadia-Hegde","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Jaslok Hospital and Research Centre, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Martinuzzi","sequence":"additional","affiliation":[{"name":"Scientific Institute, IRCCS E. Medea, Unit\u00e0 Operativa Conegliano, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hirst","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Perlman","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Takiyama","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Yamanashi, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Xiromerisiou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Papageorgiou Hospital, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Vill","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Developmental Medicine, Dr. v. 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dacruz-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Neurolog\u00eda Pedi\u00e1trica, Complexo Hospitalario Universitario, Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Smol","sequence":"additional","affiliation":[{"name":"CHU Lille, Institut de G\u00e9n\u00e9tique M\u00e9dicale, RADEME, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Ghoumid","sequence":"additional","affiliation":[{"name":"CHU Lille, Institut de G\u00e9n\u00e9tique M\u00e9dicale, RADEME, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Miguel","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Gen\u00e9tica M\u00e9dica, Universidade Federal da Bahia, Salvador, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Heine","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Ulrich","family":"Schlump","sequence":"additional","affiliation":[{"name":"Pediatrics, Evangelisches Krankenhaus Oberhausen, Oberhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Langen","sequence":"additional","affiliation":[{"name":"Sozialp\u00e4diatrisches Zentrum Hannover, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Baets","sequence":"additional","affiliation":[{"name":"Neurogenetics Group and Neuromuscular Reference Center, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Bulk","sequence":"additional","affiliation":[{"name":"Medical Genetics, Centre Hospitalier Universitaire de Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Darvish","sequence":"additional","affiliation":[{"name":"Cancer Research Center and Department of Medical Genetics, Semnan University of Medical Sciences, Semnan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somayeh","family":"Bakhtiari","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C","family":"Kruer","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Lim-Melia","sequence":"additional","affiliation":[{"name":"Pediatric Medical Genetics, Maria Fareri Children's Hospital, Valhalla, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur","family":"Aydinli","sequence":"additional","affiliation":[{"name":"Pediatric Genetics, Department of Pediatrics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Alanay","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Istanbul Medical Faculty, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia","family":"El-Rashidy","sequence":"additional","affiliation":[{"name":"Pediatrics, Ain Shams University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Nampoothiri","sequence":"additional","affiliation":[{"name":"Amrita Institute of Medical Sciences and Research Centre, Cochin, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirag","family":"Patel","sequence":"additional","affiliation":[{"name":"Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beetz","sequence":"additional","affiliation":[{"name":"Centogene AG, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bauer","sequence":"additional","affiliation":[{"name":"Centogene AG, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Guillot","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Hospital for Sick Children and The University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Hospital for Sick Children and The University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bourinaris","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Robelin","sequence":"additional","affiliation":[{"name":"Service de Neurologie, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Anheim","sequence":"additional","affiliation":[{"name":"Service de Neurologie, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah S","family":"Alamri","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel A H","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Pediatrics, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soroor","family":"Inaloo","sequence":"additional","affiliation":[{"name":"Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parham","family":"Habibzadeh","sequence":"additional","affiliation":[{"name":"Persian BayanGene Research and Training Center, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ali","family":"Faghihi","sequence":"additional","affiliation":[{"name":"Persian BayanGene Research and Training Center, Shiraz University of Medical Sciences, Shiraz, Iran"},{"name":"Center for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C","family":"Jansen","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Brock","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Roubertie","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, CHU Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil T","family":"Darras","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj B","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Divisions of Newborn Medicine and Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo M","family":"Santorelli","sequence":"additional","affiliation":[{"name":"Molecular Medicine, IRCCS Fondazione Stella Maris, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha S","family":"Zaki","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah I","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Translational Neuroscience, Celgene, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T","family":"Bennett","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,26]]},"reference":[{"key":"2020092610543930600_awz307-B1","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.ajhg.2011.04.019","article-title":"Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature","volume":"88","author":"Abou Jamra","year":"2011","journal-title":"Am J Hum Genet"},{"key":"2020092610543930600_awz307-B2","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1002\/ajmg.a.38628","article-title":"A novel homozygous AP4B1 mutation in two brothers with AP-4 deficiency syndrome and ocular anomalies","volume":"176","author":"Accogli","year":"2018","journal-title":"Am J Med Genet A"},{"key":"2020092610543930600_awz307-B3","doi-asserted-by":"crossref","first-page":"13145","DOI":"10.1074\/jbc.M010591200","article-title":"Signal-binding 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