{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:50:05Z","timestamp":1769604605630,"version":"3.49.0"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T00:00:00Z","timestamp":1396483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>Adaptor protein complex\u20104 (AP4) is a component of intracellular transportation of proteins, which is thought to have a unique role in neurons. Recently, mutations affecting all four subunits of AP4 (<jats:italic>AP4M1<\/jats:italic>, <jats:italic>AP4E1<\/jats:italic>, <jats:italic>AP4S1<\/jats:italic>, and <jats:italic>AP4B1<\/jats:italic>) have been found to cause similar autosomal recessive phenotype consisting of tetraplegic cerebral palsy and intellectual disability. The aim of this study was analyzing AP4 genes in three new families with this phenotype, and discussing their clinical findings with an emphasis on neuroimaging and facial features. Using homozygosity mapping followed by whole\u2010exome sequencing, we identified two novel homozygous mutations in <jats:italic>AP4M1<\/jats:italic> and a homozygous deletion in <jats:italic>AP4B1<\/jats:italic> in three pairs of siblings. Spastic tetraplegia, microcephaly, severe intellectual disability, limited speech, and stereotypic laughter were common findings in our patients. All patients also had similar facial features consisting of coarse and hypotonic face, bitemporal narrowing, bulbous nose with broad nasal ridge, and short philtrum which were not described in patients with <jats:italic>AP4M1<\/jats:italic> and <jats:italic>AP4B1<\/jats:italic> mutations previously. The patients presented here and previously with <jats:italic>AP4M1<\/jats:italic>, <jats:italic>AP4B1<\/jats:italic>, and <jats:italic>AP4E1<\/jats:italic> mutations shared brain abnormalities including asymmetrical ventriculomegaly, thin splenium of the corpus callosum, and reduced white matter volume. The patients also had hippocampal globoid formation and thin hippocampus. In conclusion, disorders due to mutations in AP4 complex have similar neurological, facial, and cranial imaging findings. Thus, these four genes encoding AP4 subunits should be screened in patients with autosomal recessive spastic tetraplegic cerebral palsy, severe intellectual disability, and stereotypic laughter, especially with the described facial and cranial MRI features. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36514","type":"journal-article","created":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T20:24:39Z","timestamp":1396556679000},"page":"1677-1685","source":"Crossref","is-referenced-by-count":58,"title":["Autosomal recessive spastic tetraplegia caused by <i>AP4M1<\/i> and <i>AP4B1<\/i> gene mutation: Expansion of the facial and neuroimaging features"],"prefix":"10.1002","volume":"164","author":[{"given":"Beyhan","family":"T\u00fcys\u00fcz","sequence":"first","affiliation":[{"name":"Department of Pediatric Genetics Cerrahpa\u015fa Medical School Istanbul University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaya","family":"Bilguvar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Program on Neurogenetics Yale School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naci","family":"Ko\u00e7er","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology Cerrahpa\u015fa Medical School Istanbul University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cengiz","family":"Yal\u00e7\u0131nkaya","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Cerrahpa\u015fa Medical School Istanbul University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Okay","family":"\u00c7a\u011flayan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Program on Neurogenetics Yale School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ece","family":"G\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics Cerrahpa\u015fa Medical School Istanbul University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sezgin","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics Cerrahpa\u015fa Medical School Istanbul University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinan","family":"\u00c7omu","sequence":"additional","affiliation":[{"name":"Private Practice Pediatric Neurology Levent Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murat","family":"G\u00fcnel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Program on Neurogenetics Yale School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,3]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.04.019"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-012-0314-0"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09327"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.03.011"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.10.2907"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910672106"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001170"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048\u2010009\u20100232\u2010y"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.078212.108"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6493"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.02.012"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2009.05.007"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.082263"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10423"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1299787"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.06.004"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36514","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36514","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36514","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T23:32:43Z","timestamp":1696548763000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,3]]},"references-count":18,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1002\/ajmg.a.36514"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36514","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,3]]}}}