{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:44:53Z","timestamp":1790685893608,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T00:00:00Z","timestamp":1485216000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Qatar National Priorities Research Project","award":["NPRP4-099-3-039"],"award-info":[{"award-number":["NPRP4-099-3-039"]}]},{"name":"Qatar Foundation Biomedical Research Program to Weill Cornell Medicine-Qatar"},{"name":"Teebi Project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Exome sequences account for only 2% of the genome and may overlook mutations causing disease. To obtain a more complete view, whole genome sequencing (WGS) was analyzed in a large consanguineous family in which members displayed autosomal recessively inherited cerebellar ataxia manifesting before 2 years of age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>WGS from blood\u2010derived genomic DNA was used for homozygosity mapping and a rare variant search. RNA from isolated blood leukocytes was used for quantitative polymerase chain reaction (PCR), RNA sequencing, and comparison of the transcriptomes of affected and unaffected family members.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WGS revealed a point mutation in noncoding RNA RNU12 that was associated with early onset cerebellar ataxia. The U12\u2010dependent minor spliceosome edits 879 known transcripts. Reverse transcriptase PCR demonstrated minor intron retention in all of 9 randomly selected RNAs from this group, and RNAseq showed splicing disruption specific to all U12\u2010type introns detected in blood monocytes from affected individuals. Moreover, 144 minor intron\u2013containing RNAs were differentially expressed, including transcripts for 3 genes previously associated with cerebellar neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Interference with particular spliceosome components, including small nuclear RNAs, cause reproducible uniquely distributed phenotypic and transcript\u2010specific effects, making this an important category of disease\u2010associated mutation. Our approach to differential expression analysis of minor intron\u2013containing genes is applicable to other diseases involving altered transcriptome processing. ANN NEUROL 2017;81:68\u201378<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24826","type":"journal-article","created":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T19:56:54Z","timestamp":1479499014000},"page":"68-78","source":"Crossref","is-referenced-by-count":102,"title":["Mutation in noncoding\n                    <scp>RNA RNU12<\/scp>\n                    causes early onset cerebellar ataxia"],"prefix":"10.1002","volume":"81","author":[{"given":"Mahmoud Fawzi","family":"Elsaid","sequence":"first","affiliation":[{"name":"Department of Pediatrics Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Chalhoub","sequence":"additional","affiliation":[{"name":"Neurogenetics Weill Cornell Medicine\u2013Qatar Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawfeg","family":"Ben\u2010Omran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Weill Cornell Medicine\u2013Qatar Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Kamel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Mohamoud","sequence":"additional","affiliation":[{"name":"Genomics Core Weill Cornell Medicine\u2013Qatar Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Al\u2010Dous","sequence":"additional","affiliation":[{"name":"Genomics Core Weill Cornell Medicine\u2013Qatar Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Al\u2010Azwani","sequence":"additional","affiliation":[{"name":"Genomics Core Weill Cornell Medicine\u2013Qatar Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel A.","family":"Malek","sequence":"additional","affiliation":[{"name":"Genomics Core Weill Cornell Medicine\u2013Qatar Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Suhre","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Weill Cornell Medicine\u2013Qatar Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Elizabeth","family":"Ross","sequence":"additional","affiliation":[{"name":"Neurogenetics Feil Family Brain and Mind Research Institute, Weill Cornell Medical College New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Abdel","family":"Aleem","sequence":"additional","affiliation":[{"name":"Neurogenetics Weill Cornell Medicine\u2013Qatar Doha Qatar"},{"name":"Neurogenetics Feil Family Brain and Mind Research Institute, Weill Cornell Medical College New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-51892-7.00021-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.438"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(01)83007-4"},{"key":"e_1_2_8_5_1","first-page":"573","article-title":"The incidence and gene frequency of ataxia\u2010telangiectasia in the United States","volume":"39","author":"Swift M","year":"1986","journal-title":"Am J Hum Genet"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1006610"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-62702-5.00014-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000438224.25600.6c"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl796"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.016"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2450"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2012.01.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.02.009"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1191\/0961203303lu360xx"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr530"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1081"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.043"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.166"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.12.6951"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.01.013"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr250"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23700"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23701"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116599"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1758"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.11.057"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.043"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201303573"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200587"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1202205"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.09.012"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.24826","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24826","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:52:49Z","timestamp":1695718369000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.24826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1002\/ana.24826"],"URL":"https:\/\/doi.org\/10.1002\/ana.24826","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1]]}}}