{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:08:35Z","timestamp":1788242915062,"version":"build-2803163510"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2017\/27\/B\/NZ5\/02223"],"award-info":[{"award-number":["2017\/27\/B\/NZ5\/02223"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009687","name":"Uniwersytet Medyczny im. Piast\u00f3w Slaskich we Wroclawiu","doi-asserted-by":"publisher","award":["SUB.E160.19.004"],"award-info":[{"award-number":["SUB.E160.19.004"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Appl Genetics"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biallelic mutations in the <jats:italic>AP4B1<\/jats:italic> gene, encoding adaptor-related protein complex 4 beta-1 subunit, have been recognized as an important cause of a group of conditions leading to adaptor-related protein complex 4 (AP4)-associated hereditary spastic paraplegia (SPG47). We describe a homozygous, known variant c.1160_1161delCA (p.Thr387fs) that was found in the largest ever group of patients coming from four families. The patients exhibited early hypotonia progressing to spastic paraplegia, microcephaly, epilepsy, and central nervous system (CNS) defects and global developmental delay that are consistent with the nature of SPG47. Our findings expand phenotypic spectrum of SPG47 to include polymorphic seizures, mild\/moderate intellectual disability, and intracerebral cysts as well as point to founder mutation in AP4 deficiency disorders in apparently non-consanguineous Polish families without shared ancestry.<\/jats:p>","DOI":"10.1007\/s13353-020-00552-w","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T06:02:27Z","timestamp":1583992947000},"page":"213-218","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["AP4B1-associated hereditary spastic paraplegia: expansion of phenotypic spectrum related to homozygous p.Thr387fs variant"],"prefix":"10.1007","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8803-646X","authenticated-orcid":false,"given":"Krzysztof","family":"Szcza\u0142uba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Mierzewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-9549","authenticated-orcid":false,"given":"Robert","family":"\u015amigiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3767-6584","authenticated-orcid":false,"given":"Joanna","family":"Kosi\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8862-3242","authenticated-orcid":false,"given":"Agnieszka","family":"Koppolu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2736-3798","authenticated-orcid":false,"given":"Anna","family":"Biernacka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7113-4434","authenticated-orcid":false,"given":"Piotr","family":"Stawi\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-1782","authenticated-orcid":false,"given":"Agnieszka","family":"Pollak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6969-0535","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Rydzanicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Rafa\u0142","family":"P\u0142oski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,12]]},"reference":[{"issue":"1","key":"552_CR1","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ejmg.2010.10.006","volume":"54","author":"A Abdel Aleem","year":"2011","unstructured":"Abdel Aleem A, Abu-Shahba N, Swistun D, Silhavy J, Bielas SL, Sattar S, Gleeson JG, Zaki MS (2011) Expanding the clinical spectrum of SPG11 gene mutations in recessive hereditary spastic paraplegia with thin corpus callosum. Eur J Med Genet 54(1):82\u201385. https:\/\/doi.org\/10.1016\/j.ejmg.2010.10.006","journal-title":"Eur J Med Genet"},{"key":"552_CR2","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/ejhg.2014.73","volume":"23","author":"H Abdollahpour","year":"2015","unstructured":"Abdollahpour H, Alawi M, Kortum F, Beckstette M, Seemanova E, Komarek V, Rosenberger G, Kutsche K (2015) An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome. Eur J Hum Genet 23:256\u2013259","journal-title":"Eur J Hum Genet"},{"key":"552_CR3","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, Eck SH, Graf E, Buchert R, Borck G, Ekici A, Brockschmidt FF, Nothen MM, Munnich A, Strom TM, Reis A, Colleaux L (2011) Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am J Hum Genet 88:788\u2013795","journal-title":"Am J Hum Genet"},{"issue":"1","key":"552_CR4","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s10048-012-0314-0","volume":"13","author":"P Bauer","year":"2012","unstructured":"Bauer P, Leshinsky-Silver E, Blumkin L, Schlipf N, Schr\u00f6der C, Schicks J, Lev D, Riess O, Lerman-Sagie T, Sch\u00f6ls L (2012 Feb) Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47). Neurogenetics. 13(1):73\u201376. https:\/\/doi.org\/10.1007\/s10048-012-0314-0","journal-title":"Neurogenetics."},{"issue":"1\u20132","key":"552_CR5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jns.2011.03.011","volume":"305","author":"L Blumkin","year":"2011","unstructured":"Blumkin L, Lerman-Sagie T, Lev D, Yosovich K, Leshinsky-Silver E (2011) A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum. J Neurol Sci 305(1\u20132):67\u201370. https:\/\/doi.org\/10.1016\/j.jns.2011.03.011","journal-title":"J Neurol Sci"},{"key":"552_CR7","doi-asserted-by":"publisher","first-page":"7278","DOI":"10.1074\/jbc.274.11.7278","volume":"274","author":"EC Dell'Angelica","year":"1999","unstructured":"Dell'Angelica EC, Mullins C, Bonifacino JS (1999) AP-4, a novel protein complex related to clathrin adaptors. J Biol Chem 274:7278\u20137285","journal-title":"J Biol Chem"},{"key":"552_CR8","doi-asserted-by":"publisher","unstructured":"Ebrahimi-Fakhari D, Cheng C, Dies K, Diplock A, Pier DB, Ryan CS, Lanpher BC, Hirst J, Chung WK, Sahin M, Rosser E, Darras B, Bennett JT, CureSPG47 (2018a) Clinical and genetic characterization of AP4B1-associated SPG47. Am J Med Genet A 176(2):311\u2013318. https:\/\/doi.org\/10.1002\/ajmg.a.38561","DOI":"10.1002\/ajmg.a.38561"},{"key":"552_CR9","first-page":"1993","volume-title":"GeneReviews\u00ae [Internet]","author":"D Ebrahimi-Fakhari","year":"2018","unstructured":"Ebrahimi-Fakhari D, Behne R, Davies AK, Hirst J (2018b) AP-4-associated hereditary spastic paraplegia. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, LJH B, Stephens K, Amemiya A (eds) GeneReviews\u00ae [Internet]. University of Washington, Seattle (WA), pp 1993\u20132019"},{"key":"552_CR10","doi-asserted-by":"publisher","first-page":"2787","DOI":"10.1091\/mbc.10.8.2787","volume":"10","author":"J Hirst","year":"1999","unstructured":"Hirst J, Bright NA, Rous B, Robinson MS (1999) Characterization of a fourth adaptor-related protein complex. Mol Biol Cell 10:2787\u20132802","journal-title":"Mol Biol Cell"},{"issue":"2","key":"552_CR11","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/tra.12028","volume":"14","author":"J Hirst","year":"2013","unstructured":"Hirst J, Irving C, Borner GH (2013 Feb) Adaptor protein complexes AP-4 and AP-5: new players in endosomal trafficking and progressive spastic paraplegia. Traffic. 14(2):153\u2013164. https:\/\/doi.org\/10.1111\/tra.12028","journal-title":"Traffic."},{"issue":"10","key":"552_CR12","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1212\/01.WNL.0000125324.32082.D9","volume":"62","author":"A Orlacchio","year":"2004","unstructured":"Orlacchio A, Gaudiello F, Totaro A, Floris R, St George-Hyslop PH, Bernardi G, Kawarai T (2004) A new SPG4 mutation in a variant form of spastic paraplegia with congenital arachnoid cysts. Neurology 62(10):1875\u20131878","journal-title":"Neurology"},{"key":"552_CR13","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.pneurobio.2017.03.007","volume":"153","author":"S Passemard","year":"2017","unstructured":"Passemard S, Perez F, Colin-Lemesre E, Rasika S, Gressens P, El Ghouzzi V (2017) Golgi trafficking defects in postnatal microcephaly: the evidence for \u201cGolgipathies\u201d. Prog Neurobiol 153:46\u201363. https:\/\/doi.org\/10.1016\/j.pneurobio.2017.03.007Review","journal-title":"Prog Neurobiol"},{"key":"552_CR14","doi-asserted-by":"crossref","unstructured":"P\u0142oski R, Pollak A, M\u00fcller S, Franaszczyk M, Michalak E, Kosi\u0144ska J, Stawi\u0144ski P, \u015apiewak M, Seggewiss H, Bili\u0144ska Z (2014) Does p.Q247X in TRIM63 cause human hypertrophic cardiomyopathy? Circ Res 114:e2\u2013e5","DOI":"10.1161\/CIRCRESAHA.114.302662"},{"key":"552_CR15","doi-asserted-by":"publisher","first-page":"3971","DOI":"10.1242\/jcs.185702","volume":"129","author":"C Progida","year":"2016","unstructured":"Progida C, Bakke O (2016) Bidirectional traffic between the Golgi and the endosomes\u2013machineries and regulation. J Cell Sci 129:3971\u20133982. https:\/\/doi.org\/10.1242\/jcs.185702","journal-title":"J Cell Sci"},{"issue":"8","key":"552_CR16","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1007\/s00018-015-2105-x","volume":"73","author":"AM Schreij","year":"2016","unstructured":"Schreij AM, Fon EA, McPherson PS (2016) Endocytic membrane trafficking and neurodegenerative disease. Cell Mol Life Sci 73(8):1529\u20131545. https:\/\/doi.org\/10.1007\/s00018-015-2105-x","journal-title":"Cell Mol Life Sci"},{"key":"552_CR17","doi-asserted-by":"crossref","unstructured":"\u015amigiel R, Sherman DL, Rydzanicz M, Walczak A, Mikolajkow D, Kr\u00f3lak-Olejnik B, Kosi\u0144ska J, Gasperowicz P, Biernacka A, Stawi\u0144ski P, Marciniak M, Andrzejewski W, Boczar M, Krajewski P, S\u0105siadek MM, Brophy PJ, P\u0142oski R (2018) Homozygous mutation in the neurofascin gene affecting the glial isoform of neurofascin causes severe neurodevelopment disorder with hypotonia, amimia and areflexia. Hum Mol Genet 27(21):3669\u20133674","DOI":"10.1093\/hmg\/ddy277"}],"container-title":["Journal of Applied Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13353-020-00552-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s13353-020-00552-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13353-020-00552-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:36:35Z","timestamp":1615509395000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s13353-020-00552-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,12]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["552"],"URL":"https:\/\/doi.org\/10.1007\/s13353-020-00552-w","relation":{},"ISSN":["1234-1983","2190-3883"],"issn-type":[{"value":"1234-1983","type":"print"},{"value":"2190-3883","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,12]]},"assertion":[{"value":"28 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Written informed consent for all the genetic studies performed in the patients and the parents was obtained from the patients\u2019 legal guardians (the parents).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethical Committee at the Warsaw Medical and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}