{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:22:47Z","timestamp":1791246167017,"version":"4.1.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T00:00:00Z","timestamp":1455753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T00:00:00Z","timestamp":1455753600000},"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>Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the <jats:italic>WFS1<\/jats:italic> gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, <jats:italic>in vivo<\/jats:italic> evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n\u2009=\u200921) and healthy and diabetic controls (n\u2009=\u200950). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain.<\/jats:p>","DOI":"10.1038\/srep21167","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T12:08:23Z","timestamp":1455797303000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Neuroimaging evidence of deficient axon myelination in Wolfram syndrome"],"prefix":"10.1038","volume":"6","author":[{"given":"Heather M.","family":"Lugar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Koller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerrel","family":"Rutlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bess A.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohsuke","family":"Kanekura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Urano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison N.","family":"Bischoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua S.","family":"Shimony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Hershey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Washington University Wolfram Syndrome Research Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Austin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Beato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Bihun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Doty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Earhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Eisenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hoekel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Karzon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Licis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Manwaring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. R.","family":"Paciorkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Pepino de Gruev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Permutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Pickett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ranck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Reiersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Tychsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Viehoever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. H.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,18]]},"reference":[{"key":"BFsrep21167_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1023\/A:1021875403463","volume":"4","author":"JAL Minton","year":"2003","unstructured":"Minton, J. A. L., Rainbow, L. A., Ricketts, C. & Barrett, T. G. Wolfram syndrome. Reviews in Endocrine & Metabolic Disorders 4, 53\u201359 (2003).","journal-title":"Reviews in Endocrine & Metabolic Disorders"},{"key":"BFsrep21167_CR2","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1016\/S0140-6736(95)92473-6","volume":"346","author":"TG Barrett","year":"1995","unstructured":"Barrett, T. G., Bundey, S. E. & Macleod, A. F. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet 346, 1458\u20131463 (1995).","journal-title":"Lancet"},{"key":"BFsrep21167_CR3","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/2441","volume":"20","author":"H Inoue","year":"1998","unstructured":"Inoue, H. et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat. Genet 20, 143\u2013148 (1998).","journal-title":"Nat. Genet"},{"key":"BFsrep21167_CR4","doi-asserted-by":"crossref","unstructured":"Chaussenot, A. et al. Neurologic features and genotype-phenotype correlation in wolfram syndrome. Ann. Neurol (2010).","DOI":"10.1002\/ana.22160"},{"key":"BFsrep21167_CR5","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/1750-1172-8-64","volume":"8","author":"BA Marshall","year":"2013","unstructured":"Marshall, B. A. et al. Phenotypic characteristics of early Wolfram syndrome. Orphanet. J Rare. Dis 8, 64, doi: 1750-1172-8-64 [pii];10.1186\/1750-1172-8-64 [doi] (2013).","journal-title":"Orphanet. J Rare. Dis"},{"key":"BFsrep21167_CR6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/gim.2012.180","volume":"15","author":"ML de Heredia","year":"2013","unstructured":"de Heredia, M. L., Cleries, R. & Nunes, V. Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype. Genet Med 15, 497\u2013506, doi: 10.1038\/gim.2012.180 (2013).","journal-title":"Genet Med"},{"key":"BFsrep21167_CR7","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/1750-1172-7-92","volume":"7","author":"KA Pickett","year":"2012","unstructured":"Pickett, K. A. et al. Early presentation of gait impairment in Wolfram Syndrome. Orphanet. J Rare. Dis 7, 92, doi: 1750-1172-7-92 [pii];10.1186\/1750-1172-7-92 [doi] (2012).","journal-title":"Orphanet. J Rare. Dis"},{"key":"BFsrep21167_CR8","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.gaitpost.2012.06.008","volume":"36","author":"KA Pickett","year":"2012","unstructured":"Pickett, K. A. et al. Balance impairment in individuals with Wolfram syndrome. Gait. Posture 36, 619\u2013624, doi: S0966-6362(12)00223-8 [pii];10.1016\/j.gaitpost.2012.06.008 [doi] (2012).","journal-title":"Gait. Posture"},{"key":"BFsrep21167_CR9","doi-asserted-by":"publisher","first-page":"e40604","DOI":"10.1371\/journal.pone.0040604","volume":"7","author":"T Hershey","year":"2012","unstructured":"Hershey, T. et al. Early brain vulnerability in Wolfram syndrome. PLoS. One 7, e40604, doi: 10.1371\/journal.pone.0040604 [doi];PONE-D-12-07466 [pii] (2012).","journal-title":"PLoS. One"},{"key":"BFsrep21167_CR10","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1093\/hmg\/10.5.477","volume":"10","author":"K Takeda","year":"2001","unstructured":"Takeda, K. et al. WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain. Human Molecular Genetics 10, 477\u2013484 (2001).","journal-title":"Human Molecular Genetics"},{"key":"BFsrep21167_CR11","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1093\/hmg\/ddh125","volume":"13","author":"H Ishihara","year":"2004","unstructured":"Ishihara, H. et al. Disruption of the WFS1 gene in mice causes progressive beta-cell loss and impaired stimulus-secretion coupling in insulin secretion. Hum. Mol. Genet 13, 1159\u20131170 (2004).","journal-title":"Hum. Mol. Genet"},{"key":"BFsrep21167_CR12","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.coph.2009.07.003","volume":"9","author":"SG, Fonseca","year":"2009","unstructured":"Fonseca, S. G., Burcin, M., Gromada, J. & Urano, F. Endoplasmic reticulum stress in beta-cells and development of diabetes. Curr. Opin. Pharmacol 9, 763\u2013770 (2009).","journal-title":"Curr. Opin. Pharmacol"},{"key":"BFsrep21167_CR13","doi-asserted-by":"publisher","first-page":"39609","DOI":"10.1074\/jbc.M507426200","volume":"280","author":"SG Fonseca","year":"2005","unstructured":"Fonseca, S. G. et al. WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells. J. Biol. Chem 280, 39609\u201339615 (2005).","journal-title":"J. Biol. Chem"},{"key":"BFsrep21167_CR14","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1172\/JCI39678","volume":"120","author":"SG Fonseca","year":"2010","unstructured":"Fonseca, S. G. et al. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells. J Clin Invest 120, 744\u2013755, doi: 10.1172\/JCI39678 (2010).","journal-title":"J Clin Invest"},{"key":"BFsrep21167_CR15","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1007\/s00125-005-1947-4","volume":"48","author":"AC Riggs","year":"2005","unstructured":"Riggs, A. C. et al. Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis. Diabetologia 48, 2313\u20132321 (2005).","journal-title":"Diabetologia"},{"key":"BFsrep21167_CR16","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s00125-009-1270-6","volume":"52","author":"M Akiyama","year":"2009","unstructured":"Akiyama, M. et al. Increased insulin demand promotes while pioglitazone prevents pancreatic beta cell apoptosis in Wfs1 knockout mice. Diabetologia 52, 653\u2013663 (2009).","journal-title":"Diabetologia"},{"key":"BFsrep21167_CR17","doi-asserted-by":"publisher","first-page":"E5292","DOI":"10.1073\/pnas.1421055111","volume":"111","author":"S Lu","year":"2014","unstructured":"Lu, S. et al. A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome. Proc. Natl. Acad. Sci. USA 111, E5292\u2013E5301, doi: 1421055111 [pii];10.1073\/pnas.1421055111 [doi] (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep21167_CR18","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/nn.2273","volume":"12","author":"W Lin","year":"2009","unstructured":"Lin, W. & Popko, B. Endoplasmic reticulum stress in disorders of myelinating cells. Nat Neurosci 12, 379\u2013385, doi: 10.1038\/nn.2273 (2009).","journal-title":"Nat Neurosci"},{"key":"BFsrep21167_CR19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00401-009-0546-8","volume":"118","author":"JB Hilson","year":"2009","unstructured":"Hilson, J. B., Merchant, S. N., Adams, J. C. & Joseph, J. T. Wolfram syndrome: a clinicopathologic correlation. Acta Neuropathologica 118, 415\u2013428 (2009).","journal-title":"Acta Neuropathologica"},{"key":"BFsrep21167_CR20","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13023-015-0282-1","volume":"10","author":"AN Bischoff","year":"2015","unstructured":"Bischoff, A. N. et al. Selective cognitive and psychiatric manifestations in Wolfram Syndrome. Orphanet. J Rare. Dis 10, 66, doi: 10.1186\/s13023-015-0282-1 [doi];10.1186\/s13023-015-0282-1 [pii] (2015).","journal-title":"Orphanet. J Rare. Dis"},{"key":"BFsrep21167_CR21","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/1750-1172-7-89","volume":"7","author":"C Nguyen","year":"2012","unstructured":"Nguyen, C. et al. Reliability and validity of the Wolfram Unified Rating Scale (WURS). Orphanet. J Rare. Dis 7, 89, doi: 1750-1172-7-89 [pii];10.1186\/1750-1172-7-89 [doi] (2012).","journal-title":"Orphanet. J Rare. Dis"},{"key":"BFsrep21167_CR22","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.jaapos.2014.07.162","volume":"18","author":"J Hoekel","year":"2014","unstructured":"Hoekel, J., Chisholm, S. A., Al-Lozi, A., Hershey, T. & Tychsen, L. Ophthalmologic correlates of disease severity in children and adolescents with Wolfram syndrome. J AAPOS 18, 461\u2013465, doi: S1091-8531(14)00449-2 [pii];10.1016\/j.jaapos.2014.07.162 [doi] (2014).","journal-title":"J AAPOS"},{"key":"BFsrep21167_CR23","doi-asserted-by":"crossref","unstructured":"Karzon, R. K. & Hullar, T. E. Audiologic and vestibular findings in Wolfram syndrome. Ear Hear 34, 809\u2013812, doi: 10.1097\/AUD.0b013e3182944db7 (2013).","DOI":"10.1097\/AUD.0b013e3182944db7"},{"key":"BFsrep21167_CR24","doi-asserted-by":"crossref","unstructured":"Wechsler, D. Wechsler Abbreviated Scale of Intelligence. (Psychological Corporation, 1999).","DOI":"10.1037\/t15170-000"},{"key":"BFsrep21167_CR25","unstructured":"Wechsler, D. Wechsler Test of Adult Reading Manual. (The Psychological Corporation, 2001)."},{"key":"BFsrep21167_CR26","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1006\/neur.1995.0011","volume":"4","author":"RL Doty","year":"1995","unstructured":"Doty, R. L., Bromley, S. M. & Stern, M. B. Olfactory testing as an aid in the diagnosis of Parkinson\u2019s disease: development of optimal discrimination criteria. Neurodegeneration 4, 93\u201397 (1995).","journal-title":"Neurodegeneration"},{"key":"BFsrep21167_CR27","doi-asserted-by":"publisher","first-page":"323","DOI":"10.2340\/16501977-0537","volume":"42","author":"F Franchignoni","year":"2010","unstructured":"Franchignoni, F., Horak, F., Godi, M., Nardone, A. & Giordano, A. Using psychometric techniques to improve the Balance Evaluation Systems Test: the mini-BESTest. J. Rehabil. Med 42, 323\u2013331 (2010).","journal-title":"J. Rehabil. Med"},{"key":"BFsrep21167_CR28","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1080\/87565640701361013","volume":"32","author":"JC Larson","year":"2007","unstructured":"Larson, J. C. et al. Effects of gender and age on motor exam in typically developing children. Dev. Neuropsychol 32, 543\u2013562, doi: 10.1080\/87565640701361013 (2007).","journal-title":"Dev. Neuropsychol"},{"key":"BFsrep21167_CR29","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1080\/09297040701370016","volume":"14","author":"MB Roeder","year":"2008","unstructured":"Roeder, M. B. et al. Left-right differences on timed motor examination in children. Child Neuropsychol 14, 249\u2013262, doi: 778890158 [pii];10.1080\/09297040701370016 [doi] (2008).","journal-title":"Child Neuropsychol"},{"key":"BFsrep21167_CR30","doi-asserted-by":"publisher","first-page":"S208","DOI":"10.1016\/j.neuroimage.2004.07.051","volume":"23","author":"SM Smith","year":"2004","unstructured":"Smith, S. M. et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23 Suppl 1, S208\u2013S219 (2004).","journal-title":"Neuroimage"},{"key":"BFsrep21167_CR31","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/hbm.10062","volume":"17","author":"SM Smith","year":"2002","unstructured":"Smith, S. M. Fast robust automated brain extraction. Hum Brain Mapp 17, 143\u2013155, doi: 10.1002\/hbm.10062 (2002).","journal-title":"Hum Brain Mapp"},{"key":"BFsrep21167_CR32","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S0896-6273(02)00569-X","volume":"33","author":"B Fischl","year":"2002","unstructured":"Fischl, B. et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33, 341\u2013355 (2002).","journal-title":"Neuron"},{"key":"BFsrep21167_CR33","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.neuroimage.2004.06.018","volume":"23","author":"RL Buckner","year":"2004","unstructured":"Buckner, R. L. et al. A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume. Neuroimage 23, 724\u2013738, doi: 10.1016\/j.neuroimage.2004.06.018 (2004).","journal-title":"Neuroimage"},{"key":"BFsrep21167_CR34","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/j.mri.2012.05.001","volume":"30","author":"A Fedorov","year":"2012","unstructured":"Fedorov, A. et al. 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson. Imaging 30, 1323\u20131341, doi: S0730-725X(12)00181-6 [pii];10.1016\/j.mri.2012.05.001 [doi] (2012).","journal-title":"Magn Reson. Imaging"},{"key":"BFsrep21167_CR35","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1006\/nimg.1998.0395","volume":"9","author":"AM Dale","year":"1999","unstructured":"Dale, A. M., Fischl, B. & Sereno, M. I. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9, 179\u2013194 (1999).","journal-title":"Neuroimage"},{"key":"BFsrep21167_CR36","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.neuroimage.2006.09.018","volume":"34","author":"TE Behrens","year":"2007","unstructured":"Behrens, T. E., Berg, H. J., Jbabdi, S., Rushworth, M. F. & Woolrich, M. W. Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? Neuroimage 34, 144\u2013155 (2007).","journal-title":"Neuroimage"},{"key":"BFsrep21167_CR37","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1016\/j.neuroimage.2006.02.024","volume":"31","author":"SM Smith","year":"2006","unstructured":"Smith, S. M. et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31, 1487\u20131505 (2006).","journal-title":"Neuroimage"},{"key":"BFsrep21167_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/hbm.1058","volume":"15","author":"TE Nichols","year":"2002","unstructured":"Nichols, T. E. & Holmes, A. P. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum. Brain Mapp 15, 1\u201325 (2002).","journal-title":"Hum. Brain Mapp"},{"key":"BFsrep21167_CR39","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1016\/j.jtcvs.2011.10.039","volume":"143","author":"C Ortinau","year":"2012","unstructured":"Ortinau, C. et al. Regional alterations in cerebral growth exist preoperatively in infants with congenital heart disease. J Thorac. Cardiovasc. Surg 143, 1264\u20131270, doi: S0022-5223(11)01158-5 [pii];10.1016\/j.jtcvs.2011.10.039 [doi] (2012).","journal-title":"J Thorac. Cardiovasc. Surg"},{"key":"BFsrep21167_CR40","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1006\/nimg.2002.1267","volume":"17","author":"SK Song","year":"2002","unstructured":"Song, S. K. et al. Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17, 1429\u20131436 (2002).","journal-title":"Neuroimage"},{"key":"BFsrep21167_CR41","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1002\/jnr.23458","volume":"92","author":"JJ Laukka","year":"2014","unstructured":"Laukka, J. J. et al. Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations. J Neurosci Res 92, 1723\u20131732, doi: 10.1002\/jnr.23458 (2014).","journal-title":"J Neurosci Res"},{"key":"BFsrep21167_CR42","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1309\/AJCPCYCH96QYPHJM","volume":"138","author":"DN Greene","year":"2012","unstructured":"Greene, D. N., Schmidt, R. L., Wilson, A. R., Freedman, M. S. & Grenache, D. G. Cerebrospinal fluid myelin basic protein is frequently ordered but has little value: a test utilization study. Am. J Clin. Pathol 138, 262\u2013272, doi: 138\/2\/262 [pii];10.1309\/AJCPCYCH96QYPHJM [doi] (2012).","journal-title":"Am. J Clin. Pathol"},{"key":"BFsrep21167_CR43","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1093\/cercor\/bhi062","volume":"15","author":"N Barnea-Goraly","year":"2005","unstructured":"Barnea-Goraly, N. et al. White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study. Cereb. Cortex 15, 1848\u20131854 (2005).","journal-title":"Cereb. Cortex"},{"key":"BFsrep21167_CR44","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1212\/WNL.42.6.1220","volume":"42","author":"TA Rando","year":"1992","unstructured":"Rando, T. A., Horton, J. C. & Layzer, R. B. Wolfram Syndrome - Evidence of A Diffuse Neurodegenerative Disease by Magnetic-Resonance-Imaging. Neurology 42, 1220\u20131224 (1992).","journal-title":"Neurology"},{"key":"BFsrep21167_CR45","unstructured":"Woolsey, T. A., Hanaway, J. & Gado, M. H. The brain atlas: A visual guide to the human central nervous system. 2nd edn, (Wiley, 2003)."},{"key":"BFsrep21167_CR46","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1002\/cne.23690","volume":"523","author":"MC Tate","year":"2015","unstructured":"Tate, M. C. et al. Postnatal growth of the human pons: a morphometric and immunohistochemical analysis. J Comp Neurol 523, 449\u2013462, doi: 10.1002\/cne.23690 (2015).","journal-title":"J Comp Neurol"},{"key":"BFsrep21167_CR47","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.devcel.2015.01.016","volume":"32","author":"KK Bercury","year":"2015","unstructured":"Bercury, K. K. & Macklin, W. B. Dynamics and mechanisms of CNS myelination. Dev Cell 32, 447\u2013458, doi: 10.1016\/j.devcel.2015.01.016 (2015).","journal-title":"Dev Cell"},{"key":"BFsrep21167_CR48","doi-asserted-by":"publisher","first-page":"E9","DOI":"10.3171\/2013.1.FOCUS12426","volume":"34","author":"HS Spader","year":"2013","unstructured":"Spader, H. S. et al. Advances in myelin imaging with potential clinical application to pediatric imaging. Neurosurg. Focus 34, E9, doi: 10.3171\/2013.1.FOCUS12426 (2013).","journal-title":"Neurosurg. Focus"},{"key":"BFsrep21167_CR49","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrn2758","volume":"11","author":"LB Merabet","year":"2010","unstructured":"Merabet, L. B. & Pascual-Leone, A. Neural reorganization following sensory loss: the opportunity of change. Nat. Rev. Neurosci 11, 44\u201352, doi: nrn2758 [pii];10.1038\/nrn2758 [doi] (2010).","journal-title":"Nat. Rev. Neurosci"},{"key":"BFsrep21167_CR50","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1093\/brain\/awq280","volume":"134","author":"PC Nopoulos","year":"2011","unstructured":"Nopoulos, P. C. et al. Smaller intracranial volume in prodromal Huntington\u2019s disease: evidence for abnormal neurodevelopment. Brain 134, 137\u2013142 (2011).","journal-title":"Brain"},{"key":"BFsrep21167_CR51","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1097\/MOP.0b013e328354ccdf","volume":"24","author":"L Rigoli","year":"2012","unstructured":"Rigoli, L. & Di Bella, C. Wolfram syndrome 1 and Wolfram syndrome 2. Curr Opin Pediatr 24, 512\u2013517, doi: 10.1097\/MOP.0b013e328354ccdf (2012).","journal-title":"Curr Opin Pediatr"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep21167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep21167","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep21167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T03:29:39Z","timestamp":1672889379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep21167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,18]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,2,24]]}},"alternative-id":["BFsrep21167"],"URL":"https:\/\/doi.org\/10.1038\/srep21167","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,18]]},"assertion":[{"value":"2 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"F.U. has a financial relationship with Ono Pharmaceutical, Takeda Pharmaceutical, and Amarantus Bioscience.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21167"}}