{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:38:48Z","timestamp":1778657928134,"version":"3.51.4"},"reference-count":12,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T00:00:00Z","timestamp":1491350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS072248"],"award-info":[{"award-number":["R01NS072248"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The genetic causes of many rare inherited motoneuron diseases and ataxias (<jats:styled-content style=\"fixed-case\">MND<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ATX<\/jats:styled-content>) remain largely unresolved, especially for sporadic patients, despite tremendous advances in gene discovery. Whole exome data is often available for patients, but it is rarely evaluated for unusual inheritance patterns, such as uniparental disomy (<jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content> is the inheritance of two copies of a chromosomal region from one parent, which may generate homozygosity for a deleterious recessive variant from only one carrier\u2010parent. Detection of <jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content>\u2010caused homozygous disease\u2010causing variants is detrimental to accurate genetic counseling. Whole\u2010exome sequencing can allow for the detection of such events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically studied the exomes of a phenotypically heterogeneous cohort of unresolved cases (<jats:italic>n<\/jats:italic>\u00a0=\u00a096 families) to reveal <jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content> events hindering a diagnosis and to evaluate the prevalence of <jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content> in recessive <jats:styled-content style=\"fixed-case\">MND<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ATX<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hereditary spastic paraplegia case harbored homozygous regions spanning 80% of chromosome 16. A homozygous disease\u2010causing mutation in the <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>35 disease gene was then identified within this region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates the ability to detect <jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content> in exome data of index patients. Our results suggest that <jats:styled-content style=\"fixed-case\">UPD<\/jats:styled-content> is a rare mechanism for recessive <jats:styled-content style=\"fixed-case\">MND<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ATX<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.285","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T04:12:23Z","timestamp":1491451943000},"page":"280-286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Uniparental disomy determined by whole\u2010exome sequencing in a spectrum of rare motoneuron diseases and ataxias"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4953-3487","authenticated-orcid":false,"given":"Dana M.","family":"Bis","sequence":"first","affiliation":[{"name":"John P. Hussman Institute for Human Genomics University of Miami Miami Florida"},{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics University of Miami Miami Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Sch\u00fcle","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics University of Miami Miami Florida"},{"name":"Center for Neurology and Hertie Institute for Clinical Brain Research Eberhard\u2010Karls\u2010University T\u00fcbingen Germany"},{"name":"German Center of Neurodegenerative Diseases (DZNE) T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Reichbauer","sequence":"additional","affiliation":[{"name":"Center for Neurology and Hertie Institute for Clinical Brain Research Eberhard\u2010Karls\u2010University T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthis","family":"Synofzik","sequence":"additional","affiliation":[{"name":"Center for Neurology and Hertie Institute for Clinical Brain Research Eberhard\u2010Karls\u2010University T\u00fcbingen Germany"},{"name":"German Center of Neurodegenerative Diseases (DZNE) T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim W.","family":"Rattay","sequence":"additional","affiliation":[{"name":"Center for Neurology and Hertie Institute for Clinical Brain Research Eberhard\u2010Karls\u2010University T\u00fcbingen Germany"},{"name":"German Center of Neurodegenerative Diseases (DZNE) T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Soehn","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Institute of Human Genetics University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"de Jonghe","sequence":"additional","affiliation":[{"name":"Neurogenetics Group Department of Molecular Genetics VIB University of Antwerp Campus Drie Eiken, Universiteitsplein 1 Antwerp 2610 Belgium"},{"name":"Department of Neurology Antwerp University Hospital Antwerp Belgium"},{"name":"Laboratories of Neurogenetics and Neuropathology Institute Born\u2010Bunge University of Antwerp Universiteitsplein 1 Antwerp 2610 Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludger","family":"Sch\u00f6ls","sequence":"additional","affiliation":[{"name":"Center for Neurology and Hertie Institute for Clinical Brain Research Eberhard\u2010Karls\u2010University T\u00fcbingen Germany"},{"name":"German Center of Neurodegenerative Diseases (DZNE) T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Z\u00fcchner","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics University of Miami Miami Florida"},{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics University of Miami Miami Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02379"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22836"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.160465.113"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.14604"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu401"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33939"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.014"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(200005)22:5<452::AID-BIES7>3.0.CO;2-K"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002843"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-004-1105-y"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.285","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.285","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T18:48:54Z","timestamp":1696531734000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,5]]},"references-count":12,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1002\/mgg3.285"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.285","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,5]]},"assertion":[{"value":"2016-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}