Screening for Variants in the PTEN Gene in ASD Patients in Saudi Arabia

  Background: Autism Spectrum Disorders (ASD) represents a group of complex developmental disorders characterized by varying degrees of delay or impairment in social interaction (e.g. poor eye contact) and communication with restricted and repetitive/stereotyped patterns. Macrocephaly was observed in ASD patients, where about 80% of ASD patients have a head circumference greater than the 50th percentile, and 20% have a head circumference above the 98th percentile. PTEN gene mutations were previously reported in individuals with ASD, mental retardation, developmental delays accompanied by macrocephaly, and to date 24 mutations in patients with ASD and macrocephaly were identified but the exact functional implications of these mutations are not fully investigated.

  Objectives: Screen the entire coding region of PTEN in ASD patients from multiplex and singleton consanguineous families from Saudi Arabia.

  Methods: The diagnosis of ASD was established by two independent evaluations by experienced clinicians utilizing DSM-IV criteria. Children were also evaluated by a multidisciplinary team specialized in evaluating children with ASD.  All clinical data including head circumference size were recorded.  The entire coding sequence of the PTEN gene was amplified and PCR products were sequenced using Sanger sequencing. Segregation of potential pathogenic variants was also investigated in family members when available. 

  Results: 48 patients diagnosed with ASD (from 9 multiplex families and 27 singleton cases) were screened for mutations in the PTEN gene. Some of these patients had macrocephaly.  A total of 15 variants identified in the samples (8 coding and 7 non-coding). Of the coding variants, 4 were previously reported while 4 variants were novel substitution mutations. The non-coding variants were 1 reported and the rest are novel intronic variants.

Conclusions: None of these variants segregated with the phenotype, indicating that they might represent polymorphisms rather than pathogenic mutations.  However, we can’t rule out the possibility that some of these variants might have an influence on this complex phenotype.