Genetics and Genomics Diagnostic Laboratory
Custom Gene Sequencing | PTEN: Autism Spectrum Disorder

PTEN Autism Spectrum Disorder Testing


Autism / Intellectual Disabilities with Macrocephaly


Autism spectrum disorders (ASD) represent a large group of developmental disorders that are characterized by deficiencies in social interactions and communication with repetitive behaviors and delayed development. While it is clear that genetics can play a role in the development of certain patients, approximately 90% of patients with ASD do not have a genetic etiology identified. Extreme macrocephaly (>3 standard deviations) have been observed in a subset of patients with ASD that have mutations in the PTEN gene. In addition, these individuals can have overlapping symptoms with PTEN- Hamartoma Tumor Syndromes such as polydactyly and pigmented macules on penis. As a result, PTEN sequencing is recommended for individuals with autism with macrocephaly.


Autism / Intellectual Disabilities with Macrocephaly

Testing Methodology  

Testing is performed by Sanger sequencing of the entire coding regions and intron / exon boundaries of the PTEN gene

Test Sensitivity  

Clinical Sensitivity  

Mutations in PTEN have been identified in approximately 10-20% of patients with autism with macrocephaly. PTEN sequencing in patients with autism with or without macrocephaly has a much lower diagnostic yield with less than 1% of patients have a mutation identified.

Analytical Sensitivity  

The majority of PTEN mutations reported in association with autism with macrocephaly are missense mutations. The sensitivity of DNA sequencing is over 99% for the detection of nucleotide changes, small deletions and insertions in the regions analyzed.

Mutations in regulatory regions or other untranslated regions are not detected by this test. Large deletions involving entire single exons or multiple exons, large insertions and other complex genetic events have been reported in PTEN and will not be identified using this test methodology. Rare primer site variants may lead to erroneous results.

Turnaround Time  

28 days


Butler, M.G., M.J. Dasouki, et al. (2005) "Subset of Individuals with Autism Spectrum Disorders and Extreme Macrocephaly Associated with Germline PTEN Tumour Suppressor Gene Mutations." Journal of Medical Genetics 42 (4): 318–21.

Buxbaum, J.D., G. Cai, et al. (2007) "Mutation Screening of the PTEN Gene in Patients with Autism Spectrum Disorders and Macrocephaly." American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics 144B (4): 484–91.

Klein, S., P. Sharifi-Hannauer, et al. (2013) "Macrocephaly as a Clinical Indicator of Genetic Subtypes in Autism." Autism Research: Official Journal of the International Society for Autism Research 6 (1): 51–6.

Lintas, C. and A.M. Persico (2008) "Autistic Phenotypes and Genetic Testing: State-of-the-Art for the Clinical Geneticist." Journal of Medical Genetics 46 (1): 1–8.

O’Roak, B.J., L. Vives, et al. (2012) "Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders." Science (New York, N.Y.) 338 (6114): 1619–22.

Schaefer, G.B. and N.J. Mendelsohn (2013) "Clinical Genetics Evaluation in Identifying the Etiology of Autism Spectrum Disorders: 2013 Guideline Revisions." Genetics in Medicine 15 (5): 399–407.