{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:03:54Z","timestamp":1793714634295,"version":"4.6.1"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:00:00Z","timestamp":1506988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:00:00Z","timestamp":1506988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across human brain development, using unique transcriptomic data from Allen Human Brain and BrainSpan atlases. Dystrophin isoforms show large changes in expression through life with pronounced differences between the foetal and adult human brain. The Dp140 isoform was expressed in the cerebral cortex only in foetal life stages, while in the cerebellum it was also expressed postnatally. The Purkinje isoform Dp427p was virtually absent. The expression of dystrophin isoforms was significantly associated with genes implicated in neurodevelopmental disorders, like autism spectrum disorders or attention-deficit hyper-activity disorders, which are known to be associated to DMD. We also identified relevant functional associations of the different isoforms, like an association with axon guidance or neuron differentiation during early development. Our results point to the crucial role of several dystrophin isoforms in the development and function of the human brain.<\/jats:p>","DOI":"10.1038\/s41598-017-12981-5","type":"journal-article","created":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T09:08:19Z","timestamp":1506503299000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":217,"title":["Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy"],"prefix":"10.1038","volume":"7","author":[{"given":"Nathalie","family":"Doorenweerd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-2149","authenticated-orcid":false,"given":"Ahmed","family":"Mahfouz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"van Putten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajaram","family":"Kaliyaperumal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A. C.","family":"t\u2019 Hoen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos G. M.","family":"Hendriksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke M.","family":"Aartsma-Rus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4572-1501","authenticated-orcid":false,"given":"Jan J. G. M.","family":"Verschuuren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik H.","family":"Niks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-1562","authenticated-orcid":false,"given":"Marcel J. T.","family":"Reinders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermien E.","family":"Kan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8269-7603","authenticated-orcid":false,"given":"Boudewijn P. F.","family":"Lelieveldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,3]]},"reference":[{"key":"12981_CR1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1017\/S0012162201000913","volume":"43","author":"S Cotton","year":"2001","unstructured":"Cotton, S., Voudouris, N. J. & Greenwood, K. M. Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance intelligence quotients. Dev. Med. Child Neurol. 43, 497\u2013501 (2001).","journal-title":"Dev. Med. Child Neurol."},{"key":"12981_CR2","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S0960-8966(06)80008-8","volume":"2","author":"C Billard","year":"1992","unstructured":"Billard, C. et al. Cognitive functions in Duchenne muscular dystrophy: a reappraisal and comparison with spinal muscular atrophy. Neuromuscul. Disord. 2, 371\u2013378 (1992).","journal-title":"Neuromuscul. Disord."},{"key":"12981_CR3","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1111\/j.1469-8749.1988.tb14556.x","volume":"30","author":"C Dorman","year":"1988","unstructured":"Dorman, C., Hurley, A. D. & D\u2019Avignon, J. Language and learning disorders of older boys with Duchenne muscular dystrophy. Dev.Med. Child Neurol. 30, 316\u2013327 (1988).","journal-title":"Dev.Med. Child Neurol."},{"key":"12981_CR4","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/0010-0277(93)90003-E","volume":"47","author":"A Castles","year":"1993","unstructured":"Castles, A. & Coltheart, M. Varieties of developmental dyslexia. Cognition 47, 149\u201380 (1993).","journal-title":"Cognition"},{"key":"12981_CR5","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1177\/0883073815570154","volume":"30","author":"R Banihani","year":"2015","unstructured":"Banihani, R. et al. Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy. J. Child Neurol. 30, 1472\u20131482 (2015).","journal-title":"J. Child Neurol."},{"key":"12981_CR6","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.nmd.2013.01.011","volume":"23","author":"M Pane","year":"2013","unstructured":"Pane, M. et al. Duchenne muscular dystrophy and epilepsy. Neuromuscul.Disord. 23, 313\u2013315 (2013).","journal-title":"Neuromuscul.Disord."},{"key":"12981_CR7","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1177\/0883073807309775","volume":"23","author":"JG Hendriksen","year":"2008","unstructured":"Hendriksen, J. G. & Vles, J. S. Neuropsychiatric disorders in males with duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive\u2013compulsive disorder. J. Child Neurol. 23, 477\u2013481 (2008).","journal-title":"J. Child Neurol."},{"key":"12981_CR8","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.nmd.2013.02.012","volume":"23","author":"M Pane","year":"2013","unstructured":"Pane, M. et al. Early neurodevelopmental assessment in Duchenne muscular dystrophy. Neuromuscul.Disord. 23, 451\u2013455 (2013).","journal-title":"Neuromuscul.Disord."},{"key":"12981_CR9","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1136\/adc.55.8.589","volume":"55","author":"M Yoshioka","year":"1980","unstructured":"Yoshioka, M., Okuno, T., Honda, Y. & Nakano, Y. Central nervous system involvement in progressive muscular dystrophy. Arch. Dis. Child. 55, 589\u201394 (1980).","journal-title":"Arch. Dis. Child."},{"key":"12981_CR10","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1177\/0883073807307975","volume":"23","author":"HK Young","year":"2008","unstructured":"Young, H. K. et al. Cognitive and psychological profile of males with Becker muscular dystrophy. J. Child Neurol. 23, 155\u2013162 (2008).","journal-title":"J. Child Neurol."},{"key":"12981_CR11","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S1090-3798(97)80042-6","volume":"1","author":"F Goodwin","year":"1997","unstructured":"Goodwin, F., Muntoni, F. & Dubowitz, V. Epilepsy in Duchenne and Becker muscular dystrophies. Eur. J. Paediatr. Neurol. 1, 115\u2013119 (1997).","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"12981_CR12","doi-asserted-by":"publisher","first-page":"13464","DOI":"10.1073\/pnas.011510597","volume":"97","author":"HL Sweeney","year":"2000","unstructured":"Sweeney, H. L. & Barton, E. R. The dystrophin-associated glycoprotein complex: what parts can you do without? Proc. Natl. Acad. Sci. USA. 97, 13464\u201313466 (2000).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"12981_CR13","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1002\/ar.22974","volume":"297","author":"D Townsend","year":"2014","unstructured":"Townsend, D. Finding the sweet spot: assembly and glycosylation of the dystrophin-associated glycoprotein complex. Anat. Rec.(Hoboken.) 297, 1694\u20131705 (2014).","journal-title":"Anat. Rec.(Hoboken.)"},{"key":"12981_CR14","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.tins.2012.04.004","volume":"35","author":"A Waite","year":"2012","unstructured":"Waite, A., Brown, S. C. & Blake, D. J. The dystrophin-glycoprotein complex in brain development and disease. Trends Neurosci. 35, 487\u2013496 (2012).","journal-title":"Trends Neurosci."},{"key":"12981_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00174","volume":"10","author":"RGF Hendriksen","year":"2016","unstructured":"Hendriksen, R. G. F. et al. Dystrophin Distribution and Expression in Human and Experimental Temporal Lobe Epilepsy. Front. Cell. Neurosci. 10, 174 (2016).","journal-title":"Front. Cell. Neurosci."},{"key":"12981_CR16","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/337076a0","volume":"337","author":"U Nudel","year":"1989","unstructured":"Nudel, U. et al. Duchenne Muscular-Dystrophy Gene-Product Is Not Identical in Muscle and Brain. Nature 337, 76\u201378 (1989).","journal-title":"Nature"},{"key":"12981_CR17","unstructured":"Lidov et al. Localization of dystrophin to postsynaptic regions of the central nervous system cortical neurons.pdf (2000)."},{"key":"12981_CR18","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1007\/BF02265272","volume":"97","author":"E Holder","year":"1996","unstructured":"Holder, E., Maeda, M. & Bies, R. D. Expression and regulation of the dystrophin Purkinje promoter in human skeletal muscle, heart, and brain. Hum. Genet. 97, 232\u2013239 (1996).","journal-title":"Hum. Genet."},{"key":"12981_CR19","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/hmg\/4.5.837","volume":"4","author":"VN Dsouza","year":"1995","unstructured":"Dsouza, V. N. et al. A Novel Dystrophin Isoform Is Required for Normal Retinal Electrophysiology. Hum. Mol. Genet. 4, 837\u2013842 (1995).","journal-title":"Hum. Mol. Genet."},{"key":"12981_CR20","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/ng0593-77","volume":"4","author":"TJ Byers","year":"1993","unstructured":"Byers, T. J., Lidov, H. G. W. & Kunkel, L. M. An Alternative Dystrophin Transcript Specific to Peripheral-Nerve. Nat. Genet. 4, 77\u201381 (1993).","journal-title":"Nat. Genet."},{"key":"12981_CR21","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1006\/bbrc.1995.2474","volume":"215","author":"GE Morris","year":"1995","unstructured":"Morris, G. E., Simmons, C. & Man, N. T. Apo-Dystrophins (Dp140 and Dp71) and Dystrophin Splicing Isoforms in Developing Brain. Biochem. Biophys. Res. Commun. 215, 361\u2013367 (1995).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"12981_CR22","doi-asserted-by":"publisher","first-page":"5346","DOI":"10.1073\/pnas.89.12.5346","volume":"89","author":"D Lederfein","year":"1992","unstructured":"Lederfein, D. et al. A 71-kilodalton protein is a major product of the Duchenne muscular dystrophy gene in brain and other nonmuscle tissues. Proc. Natl. Acad. Sci. USA 89, 5346\u20135350 (1992).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"12981_CR23","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1093\/hmg\/4.9.1475","volume":"4","author":"RC Austin","year":"1995","unstructured":"Austin, R. C., Howard, P. L., D\u2019Souza, V. N., Klamut, H. J. & Ray, P. N. Cloning and characterization of alternatively spliced isoforms of Dp71. Hum. Mol. Genet. 4, 1475\u20131483 (1995).","journal-title":"Hum. Mol. Genet."},{"key":"12981_CR24","doi-asserted-by":"crossref","unstructured":"Taylor, P. J. et al. Dystrophin Gene Mutation Location and the Risk of Cognitive Impairment in Duchenne Muscular Dystrophy. PLoS One 5 (2010).","DOI":"10.1371\/journal.pone.0008803"},{"key":"12981_CR25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2478\/bjmg-2013-0014","volume":"16","author":"T Chamova","year":"2013","unstructured":"Chamova, T. et al. Association Between Loss of Dp140 and Cognitive Impairment in Duchenne and Becker Dystrophies. Balk. J. Med. Genet. 16, 21\u201329 (2013).","journal-title":"Balk. J. Med. Genet."},{"key":"12981_CR26","doi-asserted-by":"crossref","unstructured":"Ricotti, V. et al. Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations. Dev. Med. Child Neurol. (2015).","DOI":"10.1111\/dmcn.12922"},{"key":"12981_CR27","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/ana.24222","volume":"76","author":"N Doorenweerd","year":"2014","unstructured":"Doorenweerd, N. et al. Reduced cerebral gray matter and altered white matter in boys with duchenne muscular dystrophy. Ann. Neurol. 76, 403\u2013411 (2014).","journal-title":"Ann. Neurol."},{"key":"12981_CR28","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/nature13185","volume":"508","author":"JA Miller","year":"2014","unstructured":"Miller, J. A. et al. Transcriptional landscape of the prenatal human brain. Nature 508, 199\u2013206 (2014).","journal-title":"Nature"},{"key":"12981_CR29","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1093\/hmg\/1.7.505","volume":"1","author":"DC Gorecki","year":"1992","unstructured":"Gorecki, D. C. et al. Expression of 4 Alternative Dystrophin Transcripts in Brain-Regions Regulated by Different Promoters. Hum. Mol. Genet. 1, 505\u2013510 (1992).","journal-title":"Hum. Mol. Genet."},{"key":"12981_CR30","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1440-1681.2007.04816.x","volume":"35","author":"SLL Kueh","year":"2008","unstructured":"Kueh, S. L. L., Head, S. I. & Morley, J. W. GABA(A) receptor expression and inhibitory post-synaptic currents in cerebellar Purkinje cells in dystrophin-deficient mdx mice. Clin. Exp. Pharmacol. Physiol. 35, 207\u201310 (2008).","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"12981_CR31","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.nlm.2013.10.017","volume":"107","author":"WM Snow","year":"2014","unstructured":"Snow, W. M., Anderson, J. E. & Fry, M. Regional and genotypic differences in intrinsic electrophysiological properties of cerebellar Purkinje neurons from wild-type and dystrophin-deficient mdx mice. Neurobiol. Learn. Mem. 107, 19\u201331 (2014).","journal-title":"Neurobiol. Learn. Mem."},{"key":"12981_CR32","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1093\/hmg\/4.3.329","volume":"4","author":"HG Lidov","year":"1995","unstructured":"Lidov, H. G., Selig, S. & Kunkel, L. M. Dp140: a novel 140 kDa CNS transcript from the dystrophin locus. Hum. Mol. Genet. 4, 329\u201335 (1995).","journal-title":"Hum. Mol. Genet."},{"key":"12981_CR33","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0306-4522(93)90392-S","volume":"54","author":"HGW Lidov","year":"1993","unstructured":"Lidov, H. G. W., Byers, T. J. & Kunkel, L. M. The Distribution of Dystrophin in the Murine Central-Nervous-System - An Immunocytochemical Study. Neuroscience 54, 167\u2013187 (1993).","journal-title":"Neuroscience"},{"key":"12981_CR34","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s10571-013-9917-8","volume":"33","author":"WM Snow","year":"2013","unstructured":"Snow, W. M., Fry, M. & Anderson, J. E. Increased density of dystrophin protein in the lateral versus the vermal mouse cerebellum. Cell Mol. Neurobiol. 33, 513\u2013520 (2013).","journal-title":"Cell Mol. Neurobiol."},{"key":"12981_CR35","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nrg3163","volume":"13","author":"B Lenhard","year":"2012","unstructured":"Lenhard, B., Sandelin, A. & Carninci, P. Metazoan promoters: emerging characteristics and insights into transcriptional regulation. Nat. Rev. Genet. 13, 233\u2013245 (2012).","journal-title":"Nat. Rev. Genet."},{"key":"12981_CR36","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0560-6","volume":"16","author":"M Lizio","year":"2015","unstructured":"Lizio, M. et al. Gateways to the FANTOM5 promoter level mammalian expression atlas. Genome.Biol. 16, 22 (2015).","journal-title":"Genome.Biol."},{"key":"12981_CR37","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1038\/nature13182","volume":"507","author":"AR Forrest","year":"2014","unstructured":"Forrest, A. R. et al. A promoter-level mammalian expression atlas. Nature 507, 462\u2013470 (2014).","journal-title":"Nature"},{"key":"12981_CR38","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nature14248","volume":"518","author":"A Kundaje","year":"2015","unstructured":"Kundaje, A. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317\u2013330 (2015).","journal-title":"Nature"},{"key":"12981_CR39","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1126\/science.1087447","volume":"302","author":"JM Stuart","year":"2003","unstructured":"Stuart, J. M., Segal, E., Koller, D. & Kim, S. K. A gene-coexpression network for global discovery of conserved genetic modules. Science (80-.). 302, 249\u2013255 (2003).","journal-title":"Science (80-.)."},{"key":"12981_CR40","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bav028","volume":"2015","author":"J Pinero","year":"2015","unstructured":"Pinero, J. et al. DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes. Database. (Oxford) 2015, bav028 (2015).","journal-title":"Database. (Oxford)"},{"key":"12981_CR41","doi-asserted-by":"crossref","unstructured":"Lidov, H. G. W. Dystrophin in the Nervous System. Brain Pathol. 63\u201377.","DOI":"10.1111\/j.1750-3639.1996.tb00783.x"},{"key":"12981_CR42","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1126\/science.aaa1934","volume":"347","author":"A Zeisel","year":"2015","unstructured":"Zeisel, A. et al. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science (80-.). 347, 1138\u201342 (2015).","journal-title":"Science (80-.)."},{"key":"12981_CR43","first-page":"1","volume":"advance on","author":"B Tasic","year":"2016","unstructured":"Tasic, B. et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. advance on, 1\u201337 (2016).","journal-title":"Nat. Neurosci."},{"key":"12981_CR44","doi-asserted-by":"crossref","unstructured":"Ricotti, V. et al. Ocular and neurodevelopmental features of Duchenne muscular dystrophy: a signature of dystrophin function in the central nervous system. Eur. J. Hum. Genet. (2015).","DOI":"10.1038\/ejhg.2015.135"},{"key":"12981_CR45","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","volume":"165","author":"Y Liu","year":"2016","unstructured":"Liu, Y. et al. On the Dependency of Cellular Protein Levels on mRNA Abundance. Cell 165, 535\u2013550 (2016).","journal-title":"Cell"},{"key":"12981_CR46","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.neubiorev.2007.09.001","volume":"32","author":"SE Cyrulnik","year":"2008","unstructured":"Cyrulnik, S. E. & Hinton, V. J. Duchenne muscular dystrophy: a cerebellar disorder? Neurosci. Biobehav. Rev. 32, 486\u201396 (2008).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"12981_CR47","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s12311-012-0355-9","volume":"11","author":"SH Fatemi","year":"2012","unstructured":"Fatemi, S. H. et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum 11, 777\u2013807 (2012).","journal-title":"Cerebellum"},{"key":"12981_CR48","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.nlm.2015.07.006","volume":"124","author":"R Chaussenot","year":"2015","unstructured":"Chaussenot, R. et al. Cognitive dysfunction in the dystrophin-deficient mouse model of Duchenne muscular dystrophy: A reappraisal from sensory to executive processes. Neurobiol. Learn. Mem. 124, 111\u2013122 (2015).","journal-title":"Neurobiol. Learn. Mem."},{"key":"12981_CR49","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.nbd.2004.05.004","volume":"17","author":"C Vaillend","year":"2004","unstructured":"Vaillend, C., Billard, J. M. & Laroche, S. Impaired long-term spatial and recognition memory and enhanced CA1 hippocampal LTP in the dystrophin-deficient Dmd(mdx) mouse. Neurobiol. Dis. 17, 10\u201320 (2004).","journal-title":"Neurobiol. Dis."},{"key":"12981_CR50","first-page":"838","volume":"24","author":"N Doorenweerd","year":"2014","unstructured":"Doorenweerd, N. et al. G.P.127 Reduced cerebral blood flow in boys with Duchenne muscular dystrophy. In. Neuromuscular Disorders 24, 838\u2013839 (2014).","journal-title":"Neuromuscular Disorders"},{"key":"12981_CR51","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.tins.2013.11.005","volume":"37","author":"N Krumm","year":"2014","unstructured":"Krumm, N., O\u2019Roak, B. J., Shendure, J. & Eichler, E. E. A de novo convergence of autism genetics and molecular neuroscience. Trends Neurosci. 37, 95\u2013105 (2014).","journal-title":"Trends Neurosci."},{"issue":"Pt 2","key":"12981_CR52","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.neuroimage.2014.08.053","volume":"102","author":"CL Goodnough","year":"2014","unstructured":"Goodnough, C. L. et al. Lack of dystrophin results in abnormal cerebral diffusion and perfusion in vivo. Neuroimage 102(Pt 2), 809\u201316 (2014).","journal-title":"Neuroimage"},{"key":"12981_CR53","doi-asserted-by":"publisher","first-page":"533","DOI":"10.2147\/DDDT.S97635","volume":"ume11","author":"KR Lim","year":"2017","unstructured":"Lim, K. R., Maruyama, R. & Yokota, T. Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Des. Devel. Ther. 11, 533\u2013545 (2017).","journal-title":"Drug Des. Devel. Ther."},{"key":"12981_CR54","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.nmd.2014.11.011","volume":"25","author":"M Haas","year":"2015","unstructured":"Haas, M. et al. European Medicines Agency review of ataluren for the treatment of ambulant patients aged 5 years and older with Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene. Neuromuscul. Disord. 25, 5\u201313 (2015).","journal-title":"Neuromuscul. Disord."},{"key":"12981_CR55","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1007\/s40265-016-0657-1","volume":"76","author":"YY Syed","year":"2016","unstructured":"Syed, Y. Y. Eteplirsen: First Global Approval. Drugs 76, 1699\u20131704 (2016).","journal-title":"Drugs"},{"key":"12981_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2017.03.024","author":"J-Z Wang","year":"2017","unstructured":"Wang, J.-Z., Wu, P., Shi, Z.-M., Xu, Y.-L. & Liu, Z.-J. The AAV-mediated and RNA-guided CRISPR\/Cas9 system for gene therapy of DMD and BMD. Brain Dev. (2017).","journal-title":"Brain Dev."},{"key":"12981_CR57","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/nm.3765","volume":"21","author":"A Goyenvalle","year":"2015","unstructured":"Goyenvalle, A. et al. Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nat. Med. 21, 270\u20135 (2015).","journal-title":"Nat. Med."},{"key":"12981_CR58","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0960-8966(02)00195-5","volume":"13","author":"JM Wheway","year":"2003","unstructured":"Wheway, J. M. & Roberts, R. G. The dystrophin lymphocyte promoter revisited: 4.5-megabase intron, or artifact? Neuromuscul.Disord. 13, 17\u201320 (2003).","journal-title":"Neuromuscul.Disord."},{"key":"12981_CR59","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/nature11405","volume":"489","author":"MJ Hawrylycz","year":"2012","unstructured":"Hawrylycz, M. J. et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489, 391\u2013399 (2012).","journal-title":"Nature"},{"key":"12981_CR60","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/humu.22758","volume":"36","author":"CL Bladen","year":"2015","unstructured":"Bladen, C. L. et al. The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations. Hum. Mutat. 36, 395\u2013402 (2015).","journal-title":"Hum. Mutat."},{"key":"12981_CR61","doi-asserted-by":"publisher","first-page":"W305","DOI":"10.1093\/nar\/gkp427","volume":"37","author":"J Chen","year":"2009","unstructured":"Chen, J., Bardes, E. E., Aronow, B. J. & Jegga, A. G. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 37, W305\u2013W311 (2009).","journal-title":"Nucleic Acids Res."},{"key":"12981_CR62","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0166-4328(01)00297-2","volume":"125","author":"Y Benjamini","year":"2001","unstructured":"Benjamini, Y., Drai, D., Elmer, G., Kafkafi, N. & Golani, I. Controlling the false discovery rate in behavior genetics research. Behav.Brain Res. 125, 279\u2013284 (2001).","journal-title":"Behav.Brain Res."},{"key":"12981_CR63","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.neuron.2012.04.009","volume":"74","author":"I Iossifov","year":"2012","unstructured":"Iossifov, I. et al. De novo gene disruptions in children on the autistic spectrum. Neuron 74, 285\u2013299 (2012).","journal-title":"Neuron"},{"key":"12981_CR64","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/nature11011","volume":"485","author":"BM Neale","year":"2012","unstructured":"Neale, B. M. et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 485, 242\u2013245 (2012).","journal-title":"Nature"},{"key":"12981_CR65","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/nature10989","volume":"485","author":"BJ O\u2019Roak","year":"2012","unstructured":"O\u2019Roak, B. J. et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485, 246\u2013250 (2012).","journal-title":"Nature"},{"key":"12981_CR66","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nature10945","volume":"485","author":"SJ Sanders","year":"2012","unstructured":"Sanders, S. J. et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485, 237\u2013241 (2012).","journal-title":"Nature"},{"key":"12981_CR67","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1056\/NEJMoa1206524","volume":"367","author":"LJ de","year":"2012","unstructured":"de, L. J. et al. Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. 367, 1921\u20131929 (2012).","journal-title":"N. Engl. J. Med."},{"key":"12981_CR68","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1016\/S0140-6736(12)61480-9","volume":"380","author":"A Rauch","year":"2012","unstructured":"Rauch, A. et al. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 380, 1674\u20131682 (2012).","journal-title":"Lancet"},{"key":"12981_CR69","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1101\/gr.178855.114","volume":"25","author":"F Hormozdiari","year":"2015","unstructured":"Hormozdiari, F., Penn, O., Borenstein, E. & Eichler, E. E. The discovery of integrated gene networks for autism and related disorders. Genome. Res. 25, 142\u2013154 (2015).","journal-title":"Genome. Res."},{"key":"12981_CR70","doi-asserted-by":"publisher","first-page":"D832","DOI":"10.1093\/nar\/gkn835","volume":"37","author":"SN Basu","year":"2009","unstructured":"Basu, S. N., Kollu, R. & Banerjee-Basu, S. AutDB: a gene reference resource for autism research. Nucleic Acids Res. 37, D832\u2013D836 (2009).","journal-title":"Nucleic Acids Res."},{"key":"12981_CR71","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1038\/nmeth.1772","volume":"8","author":"X Zhou","year":"2011","unstructured":"Zhou, X. et al. The Human Epigenome Browser at Washington University. Nat. Methods 8, 989\u2013990 (2011).","journal-title":"Nat. Methods"},{"key":"12981_CR72","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp045","volume":"37","author":"JM Ruijter","year":"2009","unstructured":"Ruijter, J. M. et al. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res. 37, e45 (2009).","journal-title":"Nucleic Acids Res."}],"updated-by":[{"DOI":"10.1038\/s41598-018-22154-7","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12981-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12981-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12981-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T08:37:11Z","timestamp":1719477431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12981-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,3]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["12981"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-12981-5","relation":{"correction":[{"id-type":"doi","id":"10.1038\/s41598-018-22154-7","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,3]]},"assertion":[{"value":"1 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2018","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"12575"}}