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

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 144B; no. 4; pp. 484 - 491
• Main Authors: Buxbaum, Joseph D., Cai, Guiqing, Chaste, Pauline, Nygren, Gudrun, Goldsmith, Juliet, Reichert, Jennifer, Anckarsäter, Henrik, Rastam, Maria, Smith, Christopher J., Silverman, Jeremy M., Hollander, Eric, Leboyer, Marion, Gillberg, Christopher, Verloes, Alain, Betancur, Catalina
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05-06-2007; Wiley-Liss
• Subjects: Abnormalities; Abnormalities, Multiple - genetics; Adolescent; Adult; Amino Acid Sequence; Asparagine; Asparagine - genetics; Aspartic Acid; Aspartic Acid - genetics; Autistic Disorder; Autistic Disorder - complications; Autistic Disorder - genetics; Bannayan-Riley-Ruvalcaba syndrome; Biological and medical sciences; Chemistry; Child; Child clinical studies; Child, Preschool; Complications; Cowden syndrome; Craniofacial Abnormalities; Craniofacial Abnormalities - complications; Craniofacial Abnormalities - genetics; Dermatology; Developmental disorders; Diseases of the osteoarticular system; DNA Mutational Analysis; Exons; Exons - genetics; Female; Genetic Testing; Genetics; Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue; Humans; Infantile autism; Introns; Introns - genetics; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; Molecular Sequence Data; Multiple; multiplex ligation-dependent probe amplification; Mutation; Mutation - genetics; polydactyly; Preschool; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psykiatri; PTEN Phosphohydrolase; PTEN Phosphohydrolase - chemistry; PTEN Phosphohydrolase - genetics; sequence analysis; Syndrome; Pseudotumor; Skin disease; Diseases of the osteoarticular system; Developmental disorder; Genital diseases; Spectrum; Cowden syndrome; Disease of the hand; Polydactyly; Upper limb; Molecular probe; sequence analysis; Benign neoplasm; Neurological disorder; Tumor suppressor gene; Human; Nervous system diseases; Dysostosis; Patient; Medical screening; Congenital disease; Hamartoma; Genetic disease; multiplex ligation-dependent probe amplification; Autism; Screening; Gene amplification; Ligature; Malformation; Digestive diseases; Mutation; Bannayan Riley Ruvalcaba syndrome; Macrocephaly; Bannayan- Riley-Ruvalcaba syndrome
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30493

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.