{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:20:51Z","timestamp":1784164851057,"version":"3.55.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T00:00:00Z","timestamp":1428451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0122966","type":"journal-article","created":{"date-parts":[[2015,4,8]],"date-time":"2015-04-08T14:21:15Z","timestamp":1428502875000},"page":"e0122966","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Functional Characterization of the spf\/ash Splicing Variation in OTC Deficiency of Mice and Man"],"prefix":"10.1371","volume":"10","author":[{"given":"Ana","family":"Rivera-Barahona","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"S\u00e1nchez-Alcudia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiu Man","family":"Viecelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"R\u00fcfenacht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Ugarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"H\u00e4berle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Th\u00f6ny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes Ruiz","family":"Desviat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,4,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/(SICI)1096-8628(19970120)68:2<236::AID-AJMG23>3.0.CO;2-U","article-title":"Asymptomatic and late-onset ornithine transcarbamylase deficiency caused by a A208T mutation: clinical, biochemical and DNA analyses in a four-generation family","volume":"68","author":"MG Ausems","year":"1997","journal-title":"Am J Med Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/1096-8628(20000814)93:4<313::AID-AJMG11>3.0.CO;2-M","article-title":"Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype","volume":"93","author":"BA McCullough","year":"2000","journal-title":"Am J Med Genet"},{"key":"ref3","article-title":"GeneReviews","author":"BC Lanpher","year":"1993"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1750-1172-7-32","article-title":"Suggested guidelines for the diagnosis and management of urea cycle disorders","volume":"7","author":"J Haberle","year":"2012","journal-title":"Orphanet J Rare Dis"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/humu.20339","article-title":"Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene","volume":"27","author":"S Yamaguchi","year":"2006","journal-title":"Hum Mutat"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ymgme.2008.11.167","article-title":"High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH","volume":"96","author":"OA Shchelochkov","year":"2009","journal-title":"Mol Genet Metab"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s10545-013-9624-0","article-title":"Cross-sectional observational study of 208 patients with non-classical urea cycle disorders","volume":"37","author":"CM Ruegger","year":"2014","journal-title":"J Inherit Metab Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.ymgme.2008.03.009","article-title":"Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency","volume":"94","author":"K Engel","year":"2008","journal-title":"Mol Genet Metab"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1073\/pnas.73.5.1693","article-title":"Abnormal ornithine carbamoyltransferase in mice having the sparse-fur mutation","volume":"73","author":"R DeMars","year":"1976","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1073\/pnas.86.11.4142","article-title":"The spfash mouse: a missense mutation in the ornithine transcarbamylase gene also causes aberrant mRNA splicing","volume":"86","author":"PE Hodges","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/0304-4165(83)90379-3","article-title":"Cell-free synthesis and transport of precursors of mutant ornithine carbamoyltransferases into mitochondria","volume":"760","author":"P Briand","year":"1983","journal-title":"Biochim Biophys Acta"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1093\/nar\/16.5.2099","article-title":"Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line","volume":"16","author":"C Cavard","year":"1988","journal-title":"Nucleic Acids Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/mt.2011.32","article-title":"Induction and prevention of severe hyperammonemia in the spfash mouse model of ornithine transcarbamylase deficiency using shRNA and rAAV-mediated gene delivery","volume":"19","author":"SC Cunningham","year":"2011","journal-title":"Mol Ther"},{"key":"ref14","first-page":"183","article-title":"Demonstration of the spf-ash mutation in Spanish patients with ornithine transcarbamylase deficiency of moderate severity","volume":"95","author":"MA Garcia-Perez","year":"1995","journal-title":"Hum Genet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.cell.2012.02.014","article-title":"Splice modulating therapies for human disease","volume":"148","author":"P Spitali","year":"2012","journal-title":"Cell"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nrd3625","article-title":"RNA therapeutics: beyond RNA interference and antisense oligonucleotides","volume":"11","author":"R Kole","year":"2012","journal-title":"Nat Rev Drug Discov"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.tig.2011.02.004","article-title":"Genetic therapies for RNA mis-splicing diseases","volume":"27","author":"SM Hammond","year":"2011","journal-title":"Trends Genet"},{"key":"ref18","first-page":"1769","article-title":"Comparative biochemistry of urea synthesis. I. Methods for the quantitative assay of urea cycle enzymes in liver","volume":"234","author":"GW Brown Jr.","year":"1959","journal-title":"J Biol Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.molmed.2012.06.006","article-title":"Pre-mRNA splicing in disease and therapeutics","volume":"18","author":"RK Singh","year":"2012","journal-title":"Trends Mol Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"911","DOI":"10.4161\/rna.20386","article-title":"Complexities of 5&apos;splice site definition: implications in clinical analyses","volume":"9","author":"L De Conti","year":"2012","journal-title":"RNA Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.ymgme.2012.05.013","article-title":"Splicing of phenylalanine hydroxylase (PAH) exon 11 is vulnerable: molecular pathology of mutations in PAH exon 11","volume":"106","author":"C Heintz","year":"2012","journal-title":"Mol Genet Metab"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1126\/science.3603027","article-title":"The molecular basis of the sparse fur mouse mutation","volume":"237","author":"G Veres","year":"1987","journal-title":"Science"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1016\/j.febslet.2006.07.018","article-title":"NF1 mRNA biogenesis: effect of the genomic milieu in splicing regulation of the NF1 exon 37 region","volume":"580","author":"M Baralle","year":"2006","journal-title":"FEBS Lett"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1101\/gr.6859308","article-title":"Features of 5&apos;-splice-site efficiency derived from disease-causing mutations and comparative genomics","volume":"18","author":"X Roca","year":"2008","journal-title":"Genome Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1136\/jmg.2004.029538","article-title":"Splicing in action: assessing disease causing sequence changes","volume":"42","author":"D Baralle","year":"2005","journal-title":"J Med Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/978-1-61779-767-5_3","article-title":"Minigenes to confirm exon skipping mutations","volume":"867","author":"LR Desviat","year":"2012","journal-title":"Methods Mol Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10545-010-9135-1","article-title":"Present and future of antisense therapy for splicing modulation in inherited metabolic disease","volume":"33","author":"B Perez","year":"2010","journal-title":"J Inherit Metab Dis"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1089\/nat.2013.0453","article-title":"Antisense mediated splicing modulation for inherited metabolic diseases: challenges for delivery","volume":"24","author":"B Perez","year":"2014","journal-title":"Nucleic Acid Ther"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.jhep.2013.05.045","article-title":"Liver as a target for oligonucleotide therapeutics","volume":"59","author":"A Sehgal","year":"2013","journal-title":"J Hepatol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/cge.12402","article-title":"Antisense-mediated therapeutic pseudoexon skipping in TMEM165-CDG","volume":"87","author":"P Yuste-Checa","year":"2015","journal-title":"Clin Genet"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1093\/hmg\/dds045","article-title":"An exon-specific U1 small nuclear RNA (snRNA) strategy to correct splicing defects","volume":"21","author":"Alanis E Fernandez","year":"2012","journal-title":"Hum Mol Genet"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/cge.12243","article-title":"Functional analysis and in vitro correction of splicing FAH mutations causing tyrosinemia type I","volume":"86","author":"R Perez-Carro","year":"2013","journal-title":"Clin Genet"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1042\/BST0360483","article-title":"Substances that can change alternative splice-site selection","volume":"36","author":"C Sumanasekera","year":"2008","journal-title":"Biochem Soc Trans"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.bbadis.2012.03.001","article-title":"Activation of a cryptic splice site in a potentially lethal coagulation defect accounts for a functional protein variant","volume":"1822","author":"N Cavallari","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.ajhg.2010.08.016","article-title":"Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs","volume":"87","author":"L Hartmann","year":"2010","journal-title":"Am J Hum Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00439-004-1147-1","article-title":"Qualitative and quantitative analysis of the effect of splicing mutations in propionic acidemia underlying non-severe phenotypes","volume":"115","author":"S Clavero","year":"2004","journal-title":"Hum Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1086\/302857","article-title":"Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome","volume":"66","author":"LB Moller","year":"2000","journal-title":"Am J Hum Genet"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10048-011-0279-4","article-title":"Genotype-phenotype correlations in sepiapterin reductase deficiency. A splicing defect accounts for a new phenotypic variant","volume":"12","author":"L Arrabal","year":"2011","journal-title":"Neurogenetics"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/humu.1380040109","article-title":"Seven new mutations in the human ornithine transcarbamylase gene","volume":"4","author":"M Tuchman","year":"1994","journal-title":"Hum Mutat"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/humu.1380030415","article-title":"Four newly identified ornithine transcarbamylase (OTC) mutations (D126G, R129H, I172M and W332X) in Japanese male patients with early-onset OTC deficiency","volume":"3","author":"T Matsuura","year":"1994","journal-title":"Hum Mutat"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/BF02185751","article-title":"Relative frequency of mutations causing ornithine transcarbamylase deficiency in 78 families","volume":"97","author":"M Tuchman","year":"1996","journal-title":"Hum Genet"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1023\/A:1005614409241","article-title":"Mutation detection in 65 families with a possible diagnosis of ornithine carbamoyltransferase deficiency including 14 novel mutations","volume":"23","author":"S Genet","year":"2000","journal-title":"J Inherit Metab Dis"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.pediatrneurol.2014.03.029","article-title":"OTC gene in ornithine transcarbamylase deficiency: clinical course and mutational spectrum in seven Korean patients","volume":"51","author":"JH Lee","year":"2014","journal-title":"Pediatr Neurol"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0128506","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T00:00:00Z","timestamp":1431993600000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0122966","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T23:47:14Z","timestamp":1566517634000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0122966"}},"subtitle":[],"editor":[{"given":"Massimo","family":"Caputi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,4,8]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0122966","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pone.0128506","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,8]]}}}