{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:38:18Z","timestamp":1791088698299,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,4,10]],"date-time":"2007-04-10T00:00:00Z","timestamp":1176163200000},"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":[[2007,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the <jats:italic>PTEN<\/jats:italic> gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan\u2013Riley\u2013Ruvalcaba syndrome, Proteus syndrome, and Lhermitte\u2013Duclos disease. In addition, <jats:italic>PTEN<\/jats:italic> mutations have been described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In this study, we screened the <jats:italic>PTEN<\/jats:italic> gene for mutations and deletions in 88 patients with ASDs and macrocephaly (defined as \u22652 SD above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions, as well as the promoter region. Dosage analysis of <jats:italic>PTEN<\/jats:italic> was carried out using multiplex ligation\u2010dependent probe amplification (MLPA). No partial or whole gene deletions were observed. We identified a de novo missense mutation (D326N) in a highly conserved amino acid in a 5\u2010year\u2010old boy with autism, mental retardation, language delay, extreme macrocephaly (+9.6 SD) and polydactyly of both feet. Polydactyly has previously been described in two patients with Lhermitte\u2013Duclos disease and CS and is thus likely to be a rare sign of <jats:italic>PTEN<\/jats:italic> mutations. Our findings suggest that <jats:italic>PTEN<\/jats:italic> mutations are a relatively infrequent cause of ASDs with macrocephaly. Screening of <jats:italic>PTEN<\/jats:italic> mutations is warranted in patients with autism and pronounced macrocephaly, even in the absence of other features of <jats:italic>PTEN<\/jats:italic>\u2010related tumor syndromes. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.30493","type":"journal-article","created":{"date-parts":[[2007,4,10]],"date-time":"2007-04-10T18:52:52Z","timestamp":1176231172000},"page":"484-491","source":"Crossref","is-referenced-by-count":243,"title":["Mutation screening of the <i>PTEN<\/i> gene in patients with autism spectrum disorders and macrocephaly"],"prefix":"10.1002","volume":"144B","author":[{"given":"Joseph 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