{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:26:51Z","timestamp":1778635611881,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T00:00:00Z","timestamp":1522627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Kwee-Seong Biomedical Research Seed Fund","award":["6903806"],"award-info":[{"award-number":["6903806"]}]},{"name":"Collaborative Research Fund grant, from the Hong Kong University Grants Committee","award":["C4014-14G"],"award-info":[{"award-number":["C4014-14G"]}]},{"name":"Pilot Project Fund","award":["4930742"],"award-info":[{"award-number":["4930742"]}]},{"name":"Brain and Mind Institute of the Chinese University of Hong Kong"},{"name":"Hong Kong PhD Fellowships,","award":["PF12-13876"],"award-info":[{"award-number":["PF12-13876"]}]},{"name":"Hong Kong PhD Fellowships,","award":["PF12-13584"],"award-info":[{"award-number":["PF12-13584"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Autism Research"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>PTEN<\/jats:italic> is a tumor suppressor gene inactivated in over 30% of human cancers. It encodes a lipid phosphatase that serves as a gatekeeper of the phosphoinositide 3\u2010kinase signaling pathway. Germline mutation frequently occurs in this gene in patients diagnosed with PTEN Hamartoma Tumor Syndrome (PHTS). PHTS individuals are characterized by macrocephaly, benign growth of multiple tissues and increased tumor risk. In addition, autistic phenotypes are found in 10\u201320% of individuals carrying the germline <jats:italic>PTEN<\/jats:italic> mutation with macrocephaly. In this report, 13 suspected PHTS patients were screened for mutation in the <jats:italic>PTEN<\/jats:italic> gene. A missense variant (c. 302T\u2009&gt;\u2009C) substituting the isoleucine at codon 101 to a threonine, a single nucleotide insertion (c. 327\u2010328insC) causing a frame shift mutation and termination at codon 109, and a nonsense variant (c. 1003C\u2009&gt;\u2009T) truncated the protein at codon 335 were identified. The I101T mutation significantly reduced PTEN protein expression levels by 2.5\u2010 to 4.0\u2010fold. Mechanistically, I101T reduced the protein half\u2010life of PTEN possibly due to enhanced polyubiquitination at Lysine 13. However, the I101T mutant retained almost 30% of the lipid phosphatase activity of the wild\u2010type protein. Finally, the I101T mutant has reduced phosphorylation at a PTEN auto\u2010dephosphorylation site at Threonine 366 and a lowered ratio of nuclear to cytosolic protein level. These partial losses of multiple PTEN biochemical functions may contribute to the tissue overgrowth and autistic features of this PHTS patient. <jats:bold><jats:italic>Autism Res<\/jats:italic><\/jats:bold> <jats:italic>2018, 11: 1098\u20131109<\/jats:italic>. \u00a9 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>The genetics of autism spectrum disorders is highly complex with individual risk influenced by both genetic and environmental factors. Mutation in the human <jats:italic>PTEN<\/jats:italic> gene confers a high risk of developing autistic behavior. This report revealed that PTEN mutations occurred in 23% of a selected group of Hong Kong patients harboring autistic features with gross overgrowth symptoms. Detailed characterization of a PTEN mutation revealed reduced protein stability as one of the underlying mechanisms responsible for reduced PTEN activity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/aur.1950","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T17:55:06Z","timestamp":1522691706000},"page":"1098-1109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Identification of a PTEN mutation with reduced protein stability, phosphatase activity, and nuclear localization in Hong Kong patients with autistic features, neurodevelopmental delays, and macrocephaly"],"prefix":"10.1002","volume":"11","author":[{"given":"Chi Wai","family":"Wong","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Lo Kwee\u2010Seong Integrated Biomedical Sciences Building The Chinese University of Hong Kong Hong Kong SAR 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For","family":"Tong","sequence":"additional","affiliation":[{"name":"Clinical Genetic Service, Department of Health Cheung Sha Wan Jockey Club Clinic Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick R.","family":"Leslie","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry, Biophysics and Bio\u2010engineering, Heriot Watt University Edinburgh Scotland UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan Fai\u2010Man","family":"Lo","sequence":"additional","affiliation":[{"name":"Clinical Genetic Service, Department of Health Cheung Sha Wan Jockey Club Clinic Hong Kong SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwong Wai","family":"Choy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Prince of Wales Hospital, The Chinese University of Hong Kong Hong Kong SAR China"},{"name":"The Chinese University of Hong Kong\u2010Baylor 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