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This study sought to characterize the neurobehavioral phenotype of <jats:italic>PTEN<\/jats:italic>-ASD. Comprehensive neurobehavioral evaluations were conducted in 36 participants (ages 3\u201321 years) with <jats:italic>PTEN<\/jats:italic>-ASD and compared to two groups of controls: non-syndromic ASD with macrocephaly (Macro-ASD, <jats:italic>n<\/jats:italic>\u2009=\u200925) and those with <jats:italic>PTEN<\/jats:italic> mutations without ASD (<jats:italic>PTEN<\/jats:italic>-no ASD, <jats:italic>n<\/jats:italic>\u2009=\u200923). Linear regression analysis or Kruskal\u2013Wallis tests were used to examine group differences on neurobehavioral measures (cognitive, behavioral, sensory, and adaptive functioning) and, for select measures, one-sample t-tests were used to compare group performance to healthy control norms. These analyses revealed a distinct neuropsychological profile associated with mutations in <jats:italic>PTEN<\/jats:italic> suggesting primary disruption of frontal lobe systems (i.e., attention, impulsivity, reaction time, processing speed, and motor coordination). Cognitive deficits in <jats:italic>PTEN<\/jats:italic>-ASD are more severe than those in <jats:italic>PTEN<\/jats:italic>-no ASD and extend to other areas of neurobehavioral function, specifically, adaptive behavior and sensory deficits. While core ASD symptoms are similar in <jats:italic>PTEN<\/jats:italic>-ASD and Macro-ASD, <jats:italic>PTEN<\/jats:italic>-ASD had lower clinical ratings of autism severity and showed more sensory abnormalities suggestive of less sensory responsiveness. Together, these results suggest that <jats:italic>PTEN<\/jats:italic>-ASD has a distinct neurobehavioral phenotype compared to idiopathic ASD that is likely to warrant special consideration for overall assessment and treatment.<\/jats:p>","DOI":"10.1038\/s41398-019-0588-1","type":"journal-article","created":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T09:02:50Z","timestamp":1570525370000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Neurobehavioral phenotype of autism spectrum disorder associated with germline heterozygous mutations in PTEN"],"prefix":"10.1038","volume":"9","author":[{"given":"Robyn M.","family":"Busch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Hogue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Frazier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Klaas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Hardan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian A.","family":"Martinez-Agosto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7044-2953","authenticated-orcid":false,"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3693-5145","authenticated-orcid":false,"given":"Charis","family":"Eng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Developmental Synaptopathies Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon K.","family":"Warfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Scherrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"Dies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajna","family":"Filip-Dhima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Gulsrud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Hanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,8]]},"reference":[{"key":"588_CR1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. 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Dr. Srivastava has no relevant financial interests or potential conflicts of interest to report. Ms. Hogue has no relevant financial interests or potential conflicts of interest to report. Dr. Frazier has received federal funding or research support from, acted as a consultant to, received travel support from, and\/or received a speaker\u2019s honorarium from the Cole Family Research Fund, Simons Foundation, Ingalls Foundation, Forest Laboratories, Ecoeos, IntegraGen, Kugona LLC, Shire Development, Bristol-Myers Squibb, Roche Pharma, National Institutes of Health, and the Brain and Behavior Research Foundation. Dr. Klaas has no relevant financial interests or potential conflicts of interest to report. Dr. Hardan has no relevant financial interests or potential conflicts of interest to report. Dr. Martinez-Agosto has no relevant financial interests or potential conflicts of interest to report. Dr. Sahin reports grant support from Novartis, Roche, Pfizer, Ipsen, LAM Therapeutics and Quadrant Biosciences, and he has served on Scientific Advisory Boards for Sage, Roche, Celgene and Takeda, all unrelated to this project. Dr. Eng has no relevant financial interests or potential conflicts of interest to report.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"253"}}