{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:01:46Z","timestamp":1791489706318,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["ZIAMH002955"],"award-info":[{"award-number":["ZIAMH002955"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Seed Grant from the Simons Center for the Social Brain at the Massachusetts Institute of Technology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Phelan\u2013McDermid syndrome (PMS), caused by either chromosome 22q13.3 deletions or pathogenic\/likely pathogenic variants in the SHANK3 gene, is a rare neurodevelopmental disorder. Behavioral issues greatly impair the quality of life for affected individuals and their families. This genotype\u2013phenotype study intended to further characterize key behavioral features and their genetic and metabolic correlates in PMS. Methods: We conducted a cross-sectional analysis of data on 56 individuals with PMS. Autistic and related behaviors were assessed with the Autism Diagnosis Interview\u2014Revised (ADI-R) and adaptive behavior skills were assessed with the Vineland Adaptive Behavior Scales-Third Edition (Vineland-3), both covering multiple aspects of communication, socialization and abnormal behaviors. Genetic diagnostic information on deletions or pathogenic variants was supplemented with the sequencing data of nine candidate genes on 22q13.3. Metabolic data were obtained using the Biolog Phenotype Mammalian MicroArray plates (PM-M). Results. Every subject in the cohort presented either prominent autistic behavior or adaptive behavior impairment, 55.4% of them meeting the ASD cutoff in every ADI-R domain and 92.9% scoring in the lowest level of adaptive behavior (range of 20\u201370). Individuals with SHANK3 variants had lower adaptive behavioral skills than those with 22q13 deletions regardless of deletion size, while genomic parameters were largely unrelated to ADI-R scores. Metabolic profiling identified unique profiles of individuals with PMS compared with controls, while distinct profiles distinguished those who met or did not meet the ADI-R ASD cutoff. Cluster analyses revealed groups of individuals with ASD and other clinical features. Conclusion. This study highlighted the importance of SHANK3 in adaptive behavioral skills and uncovered potential metabolic biomarkers of therapeutic relevance.<\/jats:p>","DOI":"10.3390\/genes17020202","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T09:41:02Z","timestamp":1770630062000},"page":"202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Behavioral Features in Phelan\u2013McDermid Syndrome: Characteristics and Genetic and Metabolic Contributions in a Cohort of 56 Individuals"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0836-6095","authenticated-orcid":false,"given":"Emily","family":"Payne","sequence":"first","affiliation":[{"name":"Healthcare Genetics and Genomics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridgette A.","family":"Moffitt","sequence":"additional","affiliation":[{"name":"Healthcare Genetics and Genomics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay M.","family":"Oberman","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Beamer","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-2800","authenticated-orcid":false,"given":"Sujata","family":"Srikanth","sequence":"additional","affiliation":[{"name":"Healthcare Genetics and Genomics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"},{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6086-4140","authenticated-orcid":false,"given":"Lauren Nicole","family":"Cascio","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Jones","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0454-5019","authenticated-orcid":false,"given":"Lavanya","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Cleveland Clinic Research, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rini","family":"Pauly","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"May","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7841-8277","authenticated-orcid":false,"given":"Cindy","family":"Skinner","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara G.","family":"DuPont","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah R.","family":"Martin","sequence":"additional","affiliation":[{"name":"Healthcare Genetics and Genomics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Curtis","family":"Rogers","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2457-6226","authenticated-orcid":false,"given":"Katy","family":"Phelan","sequence":"additional","affiliation":[{"name":"Genetics Department, Florida Cancer Specialists & Research Institute, Fort Myers, FL 33905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1625-7404","authenticated-orcid":false,"given":"Sara M.","family":"Sarasua","sequence":"additional","affiliation":[{"name":"Healthcare Genetics and Genomics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8561-8453","authenticated-orcid":false,"given":"Walter E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"},{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-4270","authenticated-orcid":false,"given":"Luigi","family":"Boccuto","sequence":"additional","affiliation":[{"name":"Healthcare Genetics and Genomics Program, School of Nursing, Clemson University, Clemson, SC 29634, USA"},{"name":"Greenwood Genetic Center, Greenwood, SC 29646, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000334260","article-title":"The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome)","volume":"2","author":"Phelan","year":"2012","journal-title":"Mol. 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