{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:34:17Z","timestamp":1791221657875,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T00:00:00Z","timestamp":1359417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Autism Research"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:p>An association between autism and macrocephaly has been previously described. A subset of cases with extreme macrocephaly (&gt;3 standard deviation [<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>], 99.7th percentile) have been correlated to mutations in the gene phosphatase and tensin homolog (<jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>). However, the phenotypic and genetic characterization of the remaining cases remains unclear. We report the phenotypic classification and genetic testing evaluation of a cohort of 33 patients with autism and macrocephaly. Within our cohort, we confirm the association of <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content> mutations and extreme macrocephaly (&gt;3 <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>, 99.7th percentile) and identify mutations in 22% of cases, including three novel <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content> mutations. In addition, we define three phenotypic subgroups: (a) those cases associated with somatic overgrowth, (b) those with disproportionate macrocephaly, and (c) those with relative macrocephaly. We have devised a novel way to segregate patients into these subgroups that will aide in the stratification of autism macrocephaly cases. Within these subgroups, we further expand the genetic etiologies for autism cases with macrocephaly by describing two novel suspected pathogenic copy number variants located at 6q23.2 and 10q24.32. These findings demonstrate the phenotypic heterogeneity of autism cases associated with macrocephaly and their genetic etiologies. The clinical yield from <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content> mutation analysis is 22% and 9% from chromosomal microarray (CMA) testing within this cohort. The identification of three distinct phenotypic subgroups within macrocephaly autism patients may allow for the identification of their respective distinct genetic etiologies that to date have remained elusive. <jats:italic><jats:bold>Autism Res<\/jats:bold> 2013, \u25cf\u25cf: \u25cf\u25cf\u2013\u25cf\u25cf.<\/jats:italic> \u00a9 2013 International Society for Autism Research, Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/aur.1266","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T20:47:45Z","timestamp":1359492465000},"page":"51-56","source":"Crossref","is-referenced-by-count":87,"title":["Macrocephaly as a Clinical Indicator of Genetic Subtypes in Autism"],"prefix":"10.1002","volume":"6","author":[{"given":"Steven","family":"Klein","sequence":"first","affiliation":[{"name":"Department of Human Genetics David Geffen School of Medicine at UCLA  Los Angeles 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