{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T21:23:24Z","timestamp":1768685004364,"version":"3.49.0"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Autosomal recessive mutations in the AP-4 (adaptor protein complex 4) complex subunit \u03f5\u00a0\u2212\u00a01 (AP-4E1) gene on chromosome 15q21.2 are known to cause spastic paraplegia 51 (SPG51). The exact phenotype of SPG51 remains poorly characterized, because only a few families have been reported as carriers of the mutation. In addition, a previous study identified an autosomal dominant mutation in the <jats:italic>AP4E1<\/jats:italic> gene as being associated with persistent stuttering. The aim of the current study was to characterize the phenotype of a paediatric patient with an identified novel <jats:italic>AP4E1<\/jats:italic> mutation presenting with significant psychomotor retardation, intellectual disability and paraplegia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Magnetic resonance imaging was used to identify hypoplasia of the corpus callosum. The DNA sample was tested using multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). In addition, next-generation sequencing (NGS) was performed using the patient\u2019s DNA, and Sanger sequencing was performed using that of his family members.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The phenotype was identified to be associated with a novel pathogenic variant c.942_943\u2009+\u20093delinsCC in the <jats:italic>AP4E1<\/jats:italic> gene. The patient manifested severely delayed psychomotor development, impaired global physical development and general illness. Movement disorders were evident during the neonatal period.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The present study identifies a previously unknown disease-inducing <jats:italic>AP4E1<\/jats:italic> gene mutation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-021-00980-5","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T08:03:18Z","timestamp":1621324998000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A new family with spastic paraplegia type 51 and novel mutations in AP4E1"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4586-1771","authenticated-orcid":false,"given":"Izabela","family":"Winkler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Miot\u0142a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Lejman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Pietrzyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Kacprzak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Kubiak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Sobczy\u0144ska-Tomaszewska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Skrzypczak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilona","family":"Jaszczuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"980_CR1","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.ajhg.2011.04.019","volume":"88","author":"R Abou Jamra","year":"2011","unstructured":"Abou Jamra R, Philippe O, Raas-Rothschild A, et al. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am J Hum Genet. 2011;88:788\u201395. https:\/\/doi.org\/10.1016\/j.ajhg.2011.04.019.","journal-title":"Am J Hum Genet"},{"key":"980_CR2","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1136\/jmg.2010.082263","volume":"48","author":"A Moreno-De-Luca","year":"2011","unstructured":"Moreno-De-Luca A, Helmers SL, Mao H, Burns TG, Melton AM, Schmidt KR, Fernhoff PM, Ledbetter DH, Martin CL. Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. J Med Genet. 2011;48:141\u20134. https:\/\/doi.org\/10.1136\/jmg.2010.082263.","journal-title":"J Med Genet"},{"key":"980_CR3","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1136\/jmg.30.1.44","volume":"30","author":"NA Fletcher","year":"1993","unstructured":"Fletcher NA, Foley J. Parental age, genetic mutation, and cerebral palsy. J Med Genet. 1993;30:44\u20136. https:\/\/doi.org\/10.1136\/jmg.30.1.44.","journal-title":"J Med Genet"},{"key":"980_CR4","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature10423","volume":"478","author":"H Najmabadi","year":"2011","unstructured":"Najmabadi H, Hu H, Garshasbi M, et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011;478:57\u201363. https:\/\/doi.org\/10.1038\/nature10423.","journal-title":"Nature"},{"key":"980_CR5","doi-asserted-by":"publisher","first-page":"7278","DOI":"10.1091\/mbc.12.7.2075","volume":"274","author":"EC Dell\u2019Angelica","year":"1999","unstructured":"Dell\u2019Angelica EC, Mullins C, Bonifacino JS. AP-4, a novel protein complex related to Clathrin adaptors. J Biol Chem. 1999;274:7278\u201385. https:\/\/doi.org\/10.1091\/mbc.12.7.2075.","journal-title":"J Biol Chem"},{"key":"980_CR6","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1111\/j.1755-3768.2010.4142.x","volume":"88","author":"AK Gerdin","year":"2010","unstructured":"Gerdin AK. The Sanger mouse genetics programme: High throughput characterisation of knockout mice. Acta Ophthalmol. 2010;88:925\u20137. https:\/\/doi.org\/10.1111\/j.1755-3768.2010.4142.x.","journal-title":"Acta Ophthalmol"},{"key":"980_CR7","unstructured":"Vergano SS, Santen G, Wieczorek D, Wollnik B, Matsumoto N, Deardorff MA. Coffin-Siris Syndrome. 2013 Apr 4 [Updated 2018 Feb 8]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132020. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK131811"},{"key":"980_CR8","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/00019605-200404000-00006","volume":"13","author":"MH Poyhonen","year":"2004","unstructured":"Poyhonen MH, Peippo MM, Valanne LK, et al. Hypertrichosis, hyperkeratosis, abnormal corpus callosum, mental retardation and dysmorphic features in three unrelated families. Clin Dysmorph. 2004;13:85\u201390. https:\/\/doi.org\/10.1097\/00019605-200404000-00006.","journal-title":"Clin Dysmorph"}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-021-00980-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-021-00980-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-021-00980-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T08:07:24Z","timestamp":1621325244000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-021-00980-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":8,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["980"],"URL":"https:\/\/doi.org\/10.1186\/s12920-021-00980-5","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,18]]},"assertion":[{"value":"9 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Bioethics Committee of the Medical University of Lublin, Lublin, Poland (KE-0254\/7\/2020). The manuscript did not contain experiments using animals. Written informed consent to participate and clinical details were obtained from the parents and patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent for publication was obtained from the parents and patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"131"}}