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We previously found reduced brain white matter volume in patients with Lesch\u2013Nyhan disease compared with healthy adults using voxel\u2010based morphometry. Here, we address the structural integrity of white matter via diffusion tensor imaging. We hypothesized that white matter integrity would be decreased in men with Lesch\u2013Nyhan disease and to a lesser extent in men with a milder variant of the disease (Lesch\u2013Nyhan variant) relative to healthy men. After acquiring diffusion\u2010weighted brain images from Lesch\u2013Nyhan disease (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095), Lesch\u2013Nyhan variant (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096) and healthy participants (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910), we used both tract\u2010based spatial statistics and a regions of interest approach to analyse between\u2010group fractional anisotropy differences. We first replicated earlier findings of reduced intracranial, grey matter and white matter volumes in patients. We then discovered marked reductions of fractional anisotropy relative to the healthy control group. The Lesch\u2013Nyhan disease group showed more pronounced reductions in white matter integrity than the Lesch\u2013Nyhan variant group. In addition to whole brain fractional anisotropy group differences, reductions in white matter integrity were observed in the corpus callosum, corona radiata, cingulum, internal capsule and superior longitudinal fasciculus. Moreover, the variant group had attenuated dystonia severity symptoms and cognitive deficits. These findings highlight the need to better understand the role of white matter in Lesch\u2013Nyhan disease.\n                  <\/jats:p>","DOI":"10.1111\/ejn.15512","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T10:24:09Z","timestamp":1636107849000},"page":"264-276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Microstructural white matter abnormalities in Lesch\u2013Nyhan disease"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-5071","authenticated-orcid":false,"given":"Victor A.","family":"Del Bene","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ainara","family":"G\u00f3mez\u2010Gastiasoro","sequence":"additional","affiliation":[{"name":"Department of Methods and Experimental Psychology University of Deusto  Bilbao Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3103-1371","authenticated-orcid":false,"given":"Tracy D.","family":"Vannorsdall","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neurology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-7573","authenticated-orcid":false,"given":"Alison","family":"Buchholz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyder A.","family":"Jinnah","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Human Genetics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-5601","authenticated-orcid":false,"given":"David J.","family":"Schretlen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Russell M. 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