GSE191274
Whole blood RNA-Seq of individuals with Sotos syndrome and healthy control subjects
To understand how NSD1 inactivation deregulates transcription, and to explore how this transcriptional deregulation affect human development, we profiled transcription in Sotos syndrome patients and healthy control individuals. Overall design: RNA-Sequencing (RNA-Seq) was applied to primary whole blood samples of individuals with Sotos syndrome (i.e., probands, n=10), and matched healthy control subjects (n=15). Ten individuals with clinical features suggestive of classic Sotos syndrome (SS) whose diagnoses were confirmed molecularly (i.e., with an NSD1 mutation or deletion) were enrolled in the study. Also enrolled were one or both (if available) parents of each SS patient (parent controls, n=16), as well as siblings of patients that were of the same sex and close to the same age of the proband (n=3). Research subjects were recruited during two separate phases, which we refer to as the 'discovery' and 'validation' phases, each including five sets of patients and matched controls. The discovery phase sample set included five SS patients that were recruited at a local child health institute. For each proband, the discovery study included one or both parents whose samples were collected and processed at the same time. For three of these probands, anonymous sex and age-matched control subjects (blood donors) were included. The validation set included five SS probands as well as a healthy control subject that was matched to the case subject by sex, ancestry (Self-declared), and age (within six years). For each proband, at least one healthy control subject was included whose sample was collected and underwent all steps of processing and analysis at the same time as the probands sample, thereby serving as technical controls. Where available, siblings were included to act as controls that were matched for demographic factors (sex, age, and ancestry), as well as family and technical factors. Where matched siblings were not available, blood samples were collected from unrelated individuals that were matched to the patient by age, sex, and self-declared ancestry (Healthy volunteer controls) (N=2). Healthy control volunteers' blood samples were collected on the same date and in the same location as the matched patient's sample. One of these healthy volunteer control subjects (ID: 5530-P) is the mother of a proband that is included in this study, whose unaffected sibling is also included. The other healthy volunteer control subject (ID: 7634-M) is the mother of a patient whose sample was not analyzed as part of this study. Where siblings or volunteer subjects were not available, blood samples of sex/age matched healthy blood donors were accessed from a local blood collection facility. Where blood donor control samples were used, a sample of a parent of the proband was also included to control for technical variables and ancestry, representing the sex-matched parent where possible (for two out of three cases). For two infant subjects, where age/sex matched siblings were not available, nor could age-matched blood donor samples be accessed (due to the patient's age), samples of both parents were included in all analysis.  See the associated publication for details of the study design.