TY - JOUR
T1 - Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly
AU - Buxbaum, Joseph D.
AU - Cai, Guiqing
AU - Chaste, Pauline
AU - Nygren, Gudrun
AU - Goldsmith, Juliet
AU - Reichert, Jennifer
AU - Anckarsäter, Henrik
AU - Rastam, Maria
AU - Smith, Christopher J.
AU - Silverman, Jeremy M.
AU - Hollander, Eric
AU - Leboyer, Marion
AU - Gillberg, Christopher
AU - Verloes, Alain
AU - Betancur, Catalina
PY - 2007/6/5
Y1 - 2007/6/5
N2 - 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.
AB - 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.
KW - Bannayan-Riley-ruvalcaba syndrome
KW - Cowden syndrome
KW - Multiplex ligation-dependent probe amplification
KW - Polydactyly
KW - Sequence analysis
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U2 - 10.1002/ajmg.b.30493
DO - 10.1002/ajmg.b.30493
M3 - Article
C2 - 17427195
AN - SCOPUS:34250812575
SN - 1552-4841
VL - 144
SP - 484
EP - 491
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 4
ER -