Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly

Joseph D. Buxbaum, Guiqing Cai, Pauline Chaste, Gudrun Nygren, Juliet Goldsmith, Jennifer Reichert, Henrik Anckarsäter, Maria Rastam, Christopher J. Smith, Jeremy M. Silverman, Eric Hollander, Marion Leboyer, Christopher Gillberg, Alain Verloes, Catalina Betancur

Research output: Contribution to journalArticlepeer-review

220 Scopus citations


Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease. In addition, PTEN mutations have been described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In this study, we screened the PTEN gene for mutations and deletions in 88 patients with ASDs and macrocephaly (denned as ≥2 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 PTEN was carried out using multiplex ligation-dependent 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-year-old 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-Duclos disease and CS and is thus likely to be a rare sign of PTEN mutations. Our findings suggest that PTEN mutations are a relatively infrequent cause of ASDs with macrocephaly. Screening of PTEN mutations is warranted in patients with autism and pronounced macrocephaly, even in the absence of other features of PTEN-related tumor syndromes.

Original languageEnglish
Pages (from-to)484-491
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number4
StatePublished - 5 Jun 2007


  • Bannayan-Riley-ruvalcaba syndrome
  • Cowden syndrome
  • Multiplex ligation-dependent probe amplification
  • Polydactyly
  • Sequence analysis


Dive into the research topics of 'Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly'. Together they form a unique fingerprint.

Cite this