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Of 86 total research participants, 38 had <jats:italic>PTEN<\/jats:italic>\u2010ASD (<jats:italic>M<\/jats:italic><jats:sub>age<\/jats:sub>\u00a0=\u20098.93\u2009years, <jats:italic>SD<\/jats:italic><jats:sub>age<\/jats:sub>\u00a0=\u20094.75), 25 Macro\u2010ASD (<jats:italic>M<\/jats:italic><jats:sub>age<\/jats:sub>\u00a0=\u200911.99\u2009years; <jats:italic>SD<\/jats:italic><jats:sub>age<\/jats:sub>\u00a0=\u20095.15), and 23 <jats:italic>PTEN<\/jats:italic>\u2010No ASD (<jats:italic>M<\/jats:italic><jats:sub>age<\/jats:sub>\u00a0=\u20098.94\u2009years; <jats:italic>SD<\/jats:italic><jats:sub>age<\/jats:sub>\u00a0=\u20094.85). The Repetitive Behavior Scale\u2010Revised (RBS\u2010R) and the Autism Diagnostic Interview\u2010Revised (ADI\u2010R) were used as measures of distinct RRB domains. There were significant group differences in the RBS\u2010R repetitive motor behaviors (RMB; <jats:italic>F<\/jats:italic>\u00a0=\u20094.52, <jats:italic>p<\/jats:italic>\u00a0=\u20090.014, <jats:italic>\u03c9<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u20090.08), insistence on sameness (IS; <jats:italic>F<\/jats:italic>\u00a0=\u20094.11, <jats:italic>p<\/jats:italic>\u00a0=\u20090.02, <jats:italic>\u03c9<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u20090.05), and circumscribed interests (CI; <jats:italic>F<\/jats:italic>\u00a0=\u20097.80, <jats:italic>p<\/jats:italic>\u00a0=\u20090.001, <jats:italic>\u03c9<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u20090.14) scales. Post hoc comparisons showed that the <jats:italic>PTEN<\/jats:italic>\u2010No ASD group had significantly lower RMB, IS, and CI scores compared to both <jats:italic>PTEN<\/jats:italic>\u2010ASD and Macro\u2010ASD groups. Importantly, <jats:italic>PTEN<\/jats:italic>\u2010No ASD group still showed elevated RRB levels. Furthermore, there was a portion of individuals in <jats:italic>PTEN<\/jats:italic>\u2010No ASD group whose Full\u2010Scale Intelligence Quotient (FSIQ) was &gt;70 that did not show floor level scores in the RMB domain. After adjusting for age and FSIQ scores, group differences were no longer statistically significant. RMB, IS, and CI domains showed distinct association patterns with sex, age, and FSIQ. This investigation provides the largest and most comprehensive characterization of distinct RRB domains in individuals with <jats:italic>PTEN<\/jats:italic> mutations to date. Despite the limitations, our findings have important assessment and treatment implications.<\/jats:p>","DOI":"10.1002\/ajmg.a.62458","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T13:21:39Z","timestamp":1629724899000},"page":"3401-3410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Toward better characterization of restricted and repetitive behaviors in individuals with germline heterozygous <scp><i>PTEN<\/i><\/scp> mutations"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7481-3923","authenticated-orcid":false,"given":"Mirko","family":"Uljarevi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Dentistry, and Health Sciences, Melbourne School of Psychological Sciences The University of Melbourne  Melbourne Victoria Australia"},{"name":"La Trobe University  Bundoora Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas W.","family":"Frazier","sequence":"additional","affiliation":[{"name":"Department of Psychology John Carroll University  University Heights Ohio USA"},{"name":"Autism Speaks  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga\u00eblle","family":"Rached","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Saint Joseph  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn M.","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Neurology Neurological Institute, Cleveland Clinic  Cleveland Ohio USA"},{"name":"Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Klaas","sequence":"additional","affiliation":[{"name":"Department of Neurology Neurological Institute, Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-1879","authenticated-orcid":false,"given":"Siddharth","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Neurology, Translational Neuroscience Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-6949","authenticated-orcid":false,"given":"Julian A.","family":"Martinez\u2010Agosto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics David Geffen School of Medicine, University of California  Los Angeles California USA"},{"name":"Division of Medical Genetics, Department of Pediatrics David Geffen School of Medicine, University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Translational Neuroscience Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Y.","family":"Hardan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Stanford University  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Developmental Synaptopathies Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0954579413000072"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0242-4"},{"issue":"247","key":"e_1_2_10_4_1","first-page":"1","article-title":"Autism genetics: Searching for specificity and convergence","volume":"13","author":"Berg J. 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