{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:17:56Z","timestamp":1790788676200,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T00:00:00Z","timestamp":1364169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>Hereditary spastic paraplegias constitute a heterogeneous group of neurodegenerative diseases encompassing pure and complicated forms, for which at least 52 loci and 31 causative genes have been identified. Although mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">SPAST<\/jats:styled-content><\/jats:italic> gene explain approximately 40% of the pure autosomal dominant forms, molecular diagnosis can be challenging for the sporadic and recessive forms, which are often complicated and clinically overlap with a broad number of movement disorders. The validity of exome sequencing as a routine diagnostic approach in the movement disorder clinic needs to be assessed. The main goal of this study was to explore the usefulness of an exome analysis for the diagnosis of a complicated form of spastic paraplegia. Whole\u2010exome sequencing was performed in two Spanish siblings with a neurodegenerative syndrome including upper and lower motor neuron, ocular and cerebellar signs. Exome sequencing revealed that both patients carry a novel homozygous nonsense mutation in exon 15 of the <jats:italic><jats:styled-content style=\"fixed-case\">SPG11<\/jats:styled-content><\/jats:italic> gene (c.<jats:styled-content style=\"fixed-case\">2678G<\/jats:styled-content>&gt;A; p.<jats:styled-content style=\"fixed-case\">W893X<\/jats:styled-content>), which was not found in 584 Spanish control chromosomes. After many years of follow\u2010up and multiple time\u2010consuming genetic testing, we were able to diagnose these patients by making use of whole\u2010exome sequencing, showing that this is a cost\u2010efficient diagnostic tool for the movement disorder specialist.<\/jats:p>","DOI":"10.1111\/cge.12133","type":"journal-article","created":{"date-parts":[[2013,2,25]],"date-time":"2013-02-25T16:37:13Z","timestamp":1361810233000},"page":"154-158","source":"Crossref","is-referenced-by-count":24,"title":["Exome sequencing is a useful diagnostic tool for complicated forms of hereditary spastic paraplegia"],"prefix":"10.1111","volume":"85","author":[{"given":"C.","family":"Bettencourt","sequence":"first","affiliation":[{"name":"Institute for Molecular and Cell Biology (IBMC) University of Porto  Porto Portugal"},{"name":"Center of Research in Natural Resources (CIRN) and Department of Biology University of the Azores  Ponta Delgada Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.L.","family":"L\u00f3pez\u2010Send\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Ram\u00f3n y Cajal  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Garc\u00eda\u2010Caldentey","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Ram\u00f3n y Cajal  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Rizzu","sequence":"additional","affiliation":[{"name":"Section of Medical Genomics, Department of Clinical Genetics VU University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.M.C.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Section of Medical Genomics, Department of Clinical Genetics VU University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Shomroni","sequence":"additional","affiliation":[{"name":"Section of Medical Genomics, Department of Clinical Genetics VU University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Quint\u00e1ns","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Publica Galega de Medicina Xen\u00f3mica and Health Research Institute of Santiago de Compostela (IDIS) Clinical Hospital of Santiago de Compostela\u2010SERGAS  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.R.","family":"D\u00e1vila","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular III, Facultad de Medicina Universidad Complutense de Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.R.","family":"Bevova","sequence":"additional","affiliation":[{"name":"Section of Medical Genomics, Department of Clinical Genetics VU University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.\u2010J.","family":"Sobrido","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Publica Galega de Medicina Xen\u00f3mica and Health Research Institute of Santiago de Compostela (IDIS) Clinical Hospital of Santiago de Compostela\u2010SERGAS  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Heutink","sequence":"additional","affiliation":[{"name":"Section of Medical Genomics, Department of Clinical Genetics VU University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"de Y\u00e9benes","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Ram\u00f3n y Cajal  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.03.025"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3282f190ba"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22148"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-0964-2"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq162"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24020"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp373"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.176601"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1980"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2011.04.004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20945"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.167528"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2010.10.006"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30928"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1299787"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2010.07.024"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01715.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.117143.110"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22235"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12133","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12133","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T16:15:17Z","timestamp":1696349717000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,25]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1111\/cge.12133"],"URL":"https:\/\/doi.org\/10.1111\/cge.12133","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,25]]}}}