The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly.
OBJECTIVE
To define the prevalence of PTEN mutations in a clinical cohort of pediatric subjects with autism spectrum disorders (ASDs), developmental delay/mental retardation (DD/MR), and/or macrocephaly and to assess genotype-phenotype correlations.


METHODS
Medical records of patients who had clinical PTEN gene sequencing ordered through our institution between January 1, 2005 and December 31, 2007 were abstracted to confirm genetic test results and medical diagnoses. Phenotypic information related to the diagnoses, prenatal history, early developmental milestones, physical characteristics, and family history for those with a confirmed PTEN mutation was also recorded.


RESULTS
One hundred fourteen patients were tested during this time period for indications of ASDs (N = 60), DD/MR (N = 49), or macrocephaly only (N = 5). Eleven mutations were identified: five in patients with ASDs and six in those with DD/MR, resulting in a prevalence of 8.3% and 12.2% in these respective clinical populations. All individuals with a PTEN mutation had significant macrocephaly (>2.0 SD) CONCLUSIONS: These data illustrate that PTEN gene sequencing has a high diagnostic yield when performed in a selected population of individuals with ASDs or DD/MR and macrocephaly. Germline mutations in PTEN are an important, identifiable etiology among these patients.
Varga
Elizabeth A
EA
Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA. elizabeth.varga@nationwidechildrens.org
Pastore
Matthew
M
Prior
Thomas
T
Herman
Gail E
GE
McBride
Kim L
KL
D001321:Autistic Disorder / Q000453:epidemiology / Q000235:genetics*; D002675:Child, Preschool; D015331:Cohort Studies; D019465:Craniofacial Abnormalities / Q000235:genetics*; D002658:Developmental Disabilities / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D015995:Prevalence
D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human