Patient 1 and his parents were enrolled in a whole genome sequencing study, approved by the Institutional Review Board of Baylor College of Medicine (BCM), Houston, USA. Enrollment in this study is not based on a particular phenotype, but rather on the referring physician’s determination that the enrolled subject likely has a genetic change in the DNA that has led to genetic disease. Patients 2–4 were referred to the Medical Genetics Laboratories at BCM for clinical whole exome sequencing. Whole exome sequencing (WES) has been offered as a clinical test at the Baylor College of Medicine Whole Genome Laboratory since October 2011. These are consecutive, unrelated samples without pre-screening criteria. The clinical WES test is not a designed study. Among the cases referred for clinical WES, 91.2% were pediatric, 8.1% were adult, and 0.7% were prenatal. 78% of the referred subjects had a history of developmental delay and/or intellectual disability, and 12.2% had a history of autism spectrum disorder.
