Novel PTEN mutations in neurodevelopmental disorders and macrocephaly

Clin Genet. 2009 Feb;75(2):195-8. doi: 10.1111/j.1399-0004.2008.01074.x. Epub 2008 Aug 26.


Somatic mutations of the phosphatase and tensin (PTEN) gene have been frequently detected in many types of human cancer. However, germline mutations can determine multiple hamartoma syndromes and, as more recently ascertained, syndromes clinically characterized by autism associated with macrocephaly. To determine whether germline mutations of PTEN may lead to different phenotypes, we screened all the nine exons of the PTEN gene in 40 patients with neurodevelopmental disorders, with or without features of autism spectrum disorder, associated with macrocephaly. Three novel de novo missense mutations were found (p.H118P, p.Y176C, p.N276S) in two severely mentally retarded patients with autism and in a subject with neurodevelopmental disorders without autistic features. Our results provide evidence that PTEN germline mutations may sustain a more wide phenotypical spectrum than previously suggested.

MeSH terms

  • Abnormalities, Multiple / genetics
  • Autistic Disorder / genetics
  • Child
  • Child, Preschool
  • Craniofacial Abnormalities / genetics*
  • Developmental Disabilities / genetics*
  • Female
  • Germ-Line Mutation*
  • Humans
  • Male
  • PTEN Phosphohydrolase / genetics*
  • Phenotype


  • PTEN Phosphohydrolase
  • PTEN protein, human