Please cite this article as follows: Buxbaum JD, Cai G, Chaste P, Nygren G, Goldsmith J, Reichert J, Anckarsäter H, Rastam M, Smith CJ, Silverman JM, Hollander E, Leboyer M, Gillberg C, Verloes A, Betancur C. 2007. Mutation Screening of the PTEN Gene in Patients With Autism Spectrum Disorders and Macrocephaly. Am J Med Genet Part B 144B:484–491.
Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly†
Version of Record online: 10 APR 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 144B, Issue 4, pages 484–491, 5 June 2007
How to Cite
Buxbaum, J. D., Cai, G., Chaste, P., Nygren, G., Goldsmith, J., Reichert, J., Anckarsäter, H., Rastam, M., Smith, C. J., Silverman, J. M., Hollander, E., Leboyer, M., Gillberg, C., Verloes, A. and Betancur, C. (2007), Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. Am. J. Med. Genet., 144B: 484–491. doi: 10.1002/ajmg.b.30493
- Issue online: 24 MAY 2007
- Version of Record online: 10 APR 2007
- Manuscript Accepted: 19 DEC 2006
- Manuscript Received: 27 SEP 2006
- Seaver Autism Research Center
- NIH. Grant Numbers: MH066673, NS-042165
- Assistance Publique-Hôpitaux de Paris
- Fondation pour la Recherche Médicale
- Fondation France Télécom
- Fondation de France
- Swedish Science Council
- Cowden syndrome;
- Bannayan–Riley–Ruvalcaba syndrome;
- sequence analysis;
- multiplex ligation-dependent probe amplification
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 (defined 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. © 2007 Wiley-Liss, Inc.