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

Buxbaum, Joseph D; Cai, Guiqing; Chaste, Pauline; Nygren, Gudrun; Goldsmith, Juliet; Reichert, Jennifer; Anckarsäter, Henrik LU ; Råstam, Maria LU ; Smith, Christopher J and Silverman, Jeremy M, et al. (2007) In American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 144B(4). p.484-491
Abstract
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 >or=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... (More)
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 >or=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. (Less)
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published
subject
keywords
multiplex ligation-dependent probe amplification, sequence analysis, polydactyly, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome
in
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
volume
144B
issue
4
pages
484 - 491
publisher
International Society of Psychiatric Genetics
external identifiers
  • pmid:17427195
  • scopus:34250812575
ISSN
1552-4841
DOI
10.1002/ajmg.b.30493
language
English
LU publication?
no
id
57dd3d3c-b28b-4788-937b-78a4f857b336 (old id 1139173)
date added to LUP
2008-08-20 10:41:03
date last changed
2017-11-05 03:43:02
@article{57dd3d3c-b28b-4788-937b-78a4f857b336,
  abstract     = {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 >or=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.},
  author       = {Buxbaum, Joseph D and Cai, Guiqing and Chaste, Pauline and Nygren, Gudrun and Goldsmith, Juliet and Reichert, Jennifer and Anckarsäter, Henrik and Råstam, Maria and Smith, Christopher J and Silverman, Jeremy M and Hollander, Eric and Leboyer, Marion and Gillberg, Christopher and Verloes, Alain and Betancur, Catalina},
  issn         = {1552-4841},
  keyword      = {multiplex ligation-dependent probe amplification,sequence analysis,polydactyly,Cowden syndrome,Bannayan-Riley-Ruvalcaba syndrome},
  language     = {eng},
  number       = {4},
  pages        = {484--491},
  publisher    = {International Society of Psychiatric Genetics},
  series       = {American Journal of Medical Genetics Part B: Neuropsychiatric Genetics},
  title        = {Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly},
  url          = {http://dx.doi.org/10.1002/ajmg.b.30493},
  volume       = {144B},
  year         = {2007},
}