{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:12:39Z","timestamp":1793747559928,"version":"4.6.1"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015940","name":"PTEN Research","doi-asserted-by":"publisher","award":["IBU\u201017\u2010001"],"award-info":[{"award-number":["IBU\u201017\u2010001"]}],"id":[{"id":"10.13039\/100015940","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Phosphatase and tensin homolog (<jats:italic>PTEN<\/jats:italic>) germline mutations are associated with cancer syndromes (<jats:italic>PTEN<\/jats:italic> hamartoma tumor syndrome; PHTS) and in pediatric patients with autism spectrum disorder (ASD) and macrocephaly. The exact prevalence of <jats:italic>PTEN<\/jats:italic> mutations in patients with ASD and macrocephaly is uncertain; with prevalence rates ranging from 1% to 17%. Most studies are retrospective and contain more adult than pediatric patients, there is a need for more prospective pediatric studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 131 patients (108\u00a0males, 23 females) with ASD and macrocephaly between the ages of 3 and 18 from five child and adolescent psychiatry clinics in Turkey from July 2018 to December 2019. We defined macrocephaly as occipito\u2010frontal HC size at or greater than 2\u00a0standard deviations (SD) above the mean for age and sex on standard growth charts. <jats:italic>PTEN<\/jats:italic> gene sequence analysis was performed using a MiSeq next generation sequencing (NGS) platform, (Illumina).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>PTEN<\/jats:italic> gene sequence analyses identified three pathogenic\/likely pathogenic mutations [NM_000314.6; p.(Pro204Leu), (p.Arg233*) and novel (p.Tyr176Cys*8)] and two variants of uncertain significance (VUS) [NM_000314.6; p.(Ala79Thr) and c.*10del]. We also report that patient with (p.Tyr176Cys*8) mutation has Grade 1\u00a0hepatosteatosis, a phenotype not previously described. This is the first <jats:italic>PTEN<\/jats:italic> prevalence study of patients with ASD and macrocephaly in Turkey and South Eastern Europe region with a largest homogenous cohort. The prevalence of <jats:italic>PTEN<\/jats:italic> mutations was found 3.8% (VUS included) or 2.29% (VUS omitted). We recommend testing for <jats:italic>PTEN<\/jats:italic> mutations in all patients with ASD and macrocephaly.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1739","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T07:45:47Z","timestamp":1626421547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Prevalence and clinical\/molecular characteristics of <i>PTEN<\/i> mutations in Turkish children with autism spectrum disorders and macrocephaly"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-7634","authenticated-orcid":false,"given":"Hande","family":"Kaymakcalan","sequence":"first","affiliation":[{"name":"Pediatric Genetics Unit Department of Pediatrics Demiroglu Bilim University Istanbul 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