Investigating the Feasibility and Implementation of Whole Genome Sequencing in Patients With Suspected Genetic Disorder

Overview

The study "Investigating the Feasibility and Implementation of Whole Genome Sequencing in Patients With Suspected Genetic Disorder" is a research study that aims to explore the use of whole genome sequencing as a potential first line genetic test for patients for which a genetic diagnosis is suspected. This is an internally funded research study. The investigators will enroll 500 participants who are being seen in one of the various genetics clinics within the Partners HealthCare system for a suspected genetic disorder for which standard-of-care genetic testing is ordered. At the time of their standard-of-care genetic testing, an extra blood sample will be collected, and genome sequencing may be performed. Within 3-4 months, patients learn if they received genome sequencing or not, and any results are returned and explained. Investigators are also studying the experiences of both participants and their providers to better understand how to implement genome sequencing into clinical care.

The goal of this research protocol is to conduct a randomized clinical trial to assess the benefits and risks of incorporating whole genome sequencing (WGS) as a first line diagnostic test in various genetic and sub-specialty clinics within a large, tertiary medical center. The investigators will enroll 500 participants within the Partners HealthCare system (e.g. Massachusetts General Hospital, Massachusetts Eye and Ear, etc.). The study will be enrolling from multiple genetics and sub-specialty clinics, including but not limited to: cardiology, GI cancer genetics, medical genetics, ataxia, endocrine genetics. Participants are eligible if their provider orders genetic testing for diagnosis of symptoms suspicious for a genetic disorder. Participants must not have had a genetic workup in the past. At the time of enrollment, a small blood sample will be obtained at the time of the participant's blood draw for standard-of-care testing. All participants will be subject to 1:1 randomization, in which 250 will receive a WGS report, and 250 will be randomized to the arm that receives standard of care testing only. Any WGS report that is generated will be incorporated into the patient's electronic medical record. For pediatric patients, the study team will attempt to collect blood samples from both biological parents when possible for trio analysis (WGS performed on the proband and both biological parents). The purpose of trio analysis is primarily for the purpose of interpreting the proband/child's results. For non-pediatric patients, saliva samples may be requested from living parents for confirmation purposes. No genetic testing reports will be generated for parents. The exception to this is if a parent of a pediatric patient (part of trio) opts to receive results from the ACMG 59 list. The participants are blinded to the arm in which they are assigned until 3-4 months from the time of consent. At that time, a study genetic counselor will call the participant to disclose the randomization assignment. If the participant was randomized to receive a WGS report, a plan will be made to review the WGS either by phone, video conferencing, or in person. After reviewing the results, the research team will write a letter to the participant summarizing the results and any relevant medical management recommendations. This letter will also include a copy of their WGS report. All participants (or their parents) will be surveyed at three points during their enrollment: baseline (at time of consent), immediately post-disclosure, and 6 months post-disclosure. The medical providers who offered the standard of care testing will also be surveyed.