{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T19:44:16Z","timestamp":1776109456354,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>White matter lesions have been described in patients with <jats:italic>PTEN<\/jats:italic> hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with <jats:italic>PTEN<\/jats:italic> mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with <jats:italic>PTEN<\/jats:italic> mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development\/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of <jats:italic>PTEN<\/jats:italic>\u2010related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32610","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T06:06:47Z","timestamp":1511158007000},"page":"101-109","source":"Crossref","is-referenced-by-count":38,"title":["Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in <i>PTEN<\/i> hamartoma tumor syndrome"],"prefix":"10.1002","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5409-8387","authenticated-orcid":false,"given":"Tugce B.","family":"Balci","sequence":"first","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Davila","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Children's Hospital of Eastern Ontario Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denice","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Children's Hospital of Eastern Ontario Ottawa Ontario Canada"},{"name":"Department of Family Medicine University of Ottawa Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Addo","family":"Boafo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Children's Hospital of Eastern Ontario Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erick","family":"Sell","sequence":"additional","affiliation":[{"name":"Division of Neurology Children's Hospital of Eastern Ontario Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Richer","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah M.","family":"Nikkel","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Ontario Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine M.","family":"Armour","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Ontario Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Tomiak","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Ontario Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew A.","family":"Lines","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada"},{"name":"Division of Metabolics and Newborn Screening Children's Hospital of Eastern Ontario Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L.","family":"Sawyer","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Ontario Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970905)71:4<489::AID-AJMG24>3.0.CO;2-B"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3680"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.024646"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30493"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.12809\/hkmj133863","article-title":"Atypical focal cortical dysplasia in a patient with Cowden syndrome","volume":"20","author":"Cheung K. M.","year":"2014","journal-title":"Hong Kong Medical Journal"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a55ef0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073811420296"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.03.005"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10257"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.10.048"},{"key":"e_1_2_7_13_1","first-page":"1","article-title":"Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism","volume":"20","author":"Frazier T. W.","year":"2014","journal-title":"Molecular Psychiatry"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0219-10.2010"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104484"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.108134"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5308.1943"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-64"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000158792.24888.d2"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1590"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.8.1461"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00035.2008"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.20"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.8.1383"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/ajmg.a.36338","article-title":"Longitudinal assessment of cognition and T2\u2010hyperintensities in NF1: An 18\u2010year study","volume":"164","author":"Payne J. M.","year":"2014","journal-title":"American Journal of Medical Genetics Part A"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.11.013"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.048934"},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/ajmg.a.36309","article-title":"Characteristic brain magnetic resonance imaging pattern in patients with macrocephaly and PTEN mutations","volume":"164","author":"Vanderver A.","year":"2014","journal-title":"American Journal of Medical Genetics Part A"},{"key":"e_1_2_7_29_1","first-page":"35","article-title":"Brain patterning perturbations following PTEN loss","volume":"7","author":"Veleva\u2010Rotse B. O.","year":"2014","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu397"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1086\/379382"}],"container-title":["American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.b.32610","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.b.32610","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T16:27:48Z","timestamp":1696004868000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.b.32610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,20]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1002\/ajmg.b.32610"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.b.32610","archive":["Portico"],"relation":{},"ISSN":["1552-4841","1552-485X"],"issn-type":[{"value":"1552-4841","type":"print"},{"value":"1552-485X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,20]]}}}