Outcomes of diagnostic exome sequencing in patients with diagnosed or suspected autism spectrum disorders

Publication date: Available online 8 February 2017
Source:Pediatric Neurology
Author(s): Mari Rossi, Dima El-Khechen, Mary Helen Black, Kelly Farwell Hagman, Sha Tang, Zoe Powis
BackgroundExome Sequencing has recently proven 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 MethodsWe performed diagnostic exome sequencing in a cohort of 163 individuals with autism spectrum disorder (ASD; 66.3%) or autistic features (33.7%).ResultsThe diagnostic yield observed in patients in our cohort was 25.8% (42/163) for positive/likely positive findings in characterized disease genes, while a candidate genetic etiology was reported for an additional 3.3% (4/120) of patients. Among the positive findings in the patients with ASD or autistic features, 61.9% were the result of de novo mutations. Patients presenting with psychiatric conditions or ataxia and/or paraplegia in addition to ASD or autistic features were significantly more likely to receive positive results compared to patients without these clinical features (95.6% vs. 27.1%, p <0.0001 83.3% vs. 21.2%, p <0.0001respectively). The majority of the positive findings were in recently identified ASD genes, supporting the importance of diagnostic exome sequencing for patients with ASD or autistic features as the causative genes might evade traditional sequential or panel testing.ConclusionsThese results suggest that diagnostic exome sequencing would be an efficient primary diagnostic method for patients with ASDs or autistic features. Moreover, our data may aid clinicians to better determine which subset of patients with ASD with additional clinical features would benefit the most from diagnostic exome sequencing.



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