Novel PTEN mutations in neurodevelopmental disorders and macrocephaly
1Molecular Medicine, Azienda Ospedaliera Universitaria Senese, Sienna, Italy. a.orrico@ao-siena.toscana.it
Clinical Genetics
|September 2, 2008
Summary
Germline mutations in the phosphatase and tensin (PTEN) gene are linked to neurodevelopmental disorders. This study identified novel PTEN mutations, expanding the known spectrum of PTEN-related phenotypes beyond autism and macrocephaly.
Area of Science:
- Genetics
- Neuroscience
- Oncology
Background:
- Somatic mutations in the phosphatase and tensin (PTEN) gene are common in human cancers.
- Germline PTEN mutations are associated with hamartoma syndromes and autism with macrocephaly.
- The full phenotypic spectrum of germline PTEN mutations remains incompletely understood.
Purpose of the Study:
- To investigate whether germline PTEN mutations contribute to a broader range of neurodevelopmental disorders.
- To screen for PTEN gene mutations in patients with neurodevelopmental disorders and macrocephaly, with or without autism spectrum disorder features.
Main Methods:
- Screening of all nine exons of the PTEN gene.
- Analysis of 40 patients diagnosed with neurodevelopmental disorders and macrocephaly.
- Identification and characterization of novel mutations.
Main Results:
- Three novel de novo missense PTEN mutations (p.H118P, p.Y176C, p.N276S) were identified.
- Mutations were found in two patients with severe intellectual disability and autism.
- A mutation was also identified in a patient with neurodevelopmental disorders but without autistic features.
Conclusions:
- Germline PTEN mutations can present with a wider phenotypic spectrum than previously recognized.
- These findings implicate PTEN in a broader range of neurodevelopmental conditions.
- Further research is warranted to fully elucidate the role of PTEN in neurodevelopment.
