Outcomes of Diagnostic Exome Sequencing in Patients With Diagnosed or Suspected Autism Spectrum Disorders

Pediatr Neurol. 2017 May;70:34-43.e2. doi: 10.1016/j.pediatrneurol.2017.01.033. Epub 2017 Feb 8.


Background: Exome sequencing has recently been proved to be a successful diagnostic method for complex neurodevelopmental disorders. However, the diagnostic yield of exome sequencing for autism spectrum disorders has not been extensively evaluated in large cohorts to date.

Materials and methods: We performed diagnostic exome sequencing in a cohort of 163 individuals with autism spectrum disorder (66.3%) or autistic features (33.7%).

Results: The diagnostic yield observed in patients in our cohort was 25.8% (42 of 163) for positive or likely positive findings in characterized disease genes, while a candidate genetic etiology was reported for an additional 3.3% (4 of 120) of patients. Among the positive findings in the patients with autism spectrum disorder or autistic features, 61.9% were the result of de novo mutations. Patients presenting with psychiatric conditions or ataxia or paraplegia in addition to autism spectrum disorder or autistic features were significantly more likely to receive positive results compared with patients without these clinical features (95.6% vs 27.1%, P < 0.0001; 83.3% vs 21.2%, P < 0.0001, respectively). The majority of the positive findings were in recently identified autism spectrum disorder genes, supporting the importance of diagnostic exome sequencing for patients with autism spectrum disorder or autistic features as the causative genes might evade traditional sequential or panel testing.

Conclusions: These results suggest that diagnostic exome sequencing would be an efficient primary diagnostic method for patients with autism spectrum disorders or autistic features. Moreover, our data may aid clinicians to better determine which subset of patients with autism spectrum disorder with additional clinical features would benefit the most from diagnostic exome sequencing.

Keywords: autism spectrum disorder; candidate genetic etiology; characterized genetic etiology; diagnostic exome sequencing.

MeSH terms

  • Autism Spectrum Disorder / diagnosis*
  • Autism Spectrum Disorder / genetics*
  • Cohort Studies
  • Exome / genetics*
  • Exome Sequencing / methods*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Mutation / genetics*