Clinical Trial: Whole Genome Medical Sequencing for Genome Discovery
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Whole Genome Medical Sequencing for Gene Discovery
Brief Summary:
Background:
- A number of rare inherited diseases affect only a few patients, and the genetic causes of these conditions remain unknown. Researchers are studying the use of a new technology called whole genome sequencing to learn which gene or genes cause these conditions. Understanding the genes that cause these diseases is important to improve diagnosis and treatment of affected patients.
Objectives:
- To identify the genetic cause of disorders that are difficult to identify with existing techniques.
- To develop best practices for the medical and counseling challenges of whole genome sequencing.
Eligibility:
- Individuals who have one of the rare disorders under consideration in this study. These conditions are generally those in which the genetic cause of the disorder is unknown. The eligibility of most individual participants will be decided on a case-by-case basis by the researchers.
- Family members of affected individuals, if that family member (often a parent) may provide genetic information.
Design:
- Participants in this study will have at least one and in some cases several of the following procedures:
- A medical genetics evaluation.
- Other tests that may include x-rays, magnetic resonance imaging (MRI) exams, and consultations with other doctors. Not all studies are necessary for each person, but the information from the tests may
Detailed Summary:
We aim to use whole-genome medical sequencing (WGMS) to discover causative molecular lesions for a set of rare, severe phenotypes hypothesized to be caused by either somatic mutations, germline de novo heterozygous mutations, germline inherited recessive, or germline inherited dominant mutations in currently unknown or uncharacterized genes. The goal of this research is threefold: to identify causative sequence variants for disorders whose molecular etiology was previously unknown, to apply this insight to both the rare disorders under study and more common phenotypes, and to enhance the study of mutation on a genome-wide level.
We plan to recruit approximately three to six affected individuals along with both parents for each phenotype under study. Prospectively recruited trios will be brought to the NIH Clinical Center for brief clinical evaluations and molecular evaluation. Each trio will be consented to whole genome sequencing with the option to learn clinically relevant results, that is, those that explain the disorder in question (what we refer to as the primary variant ) as well as other clinically relevant findings discovered incidentally as part of the WGMS process (what we refer to as secondary variants ). Participants will be offered a return visit to NIH to learn these results, and will be asked to complete surveys and participate in interviews related to their decisions about participation in the study and to learn individual genotype results.
The NIH Intramural Sequencing Center (NISC) will screen for sequence variants that conform to the hypothesized inheritance pattern. These variants will be validated, for example by using trios for de novo phenotypes, or with additional cases. We have started developing analytic algorithms to distinguish potentially pathogenic genetic alterations from normal variation. Al
Sponsor: National Human Genome Research Institute (NHGRI)
Current Primary Outcome: Indentification of molecular etiology of genetic disorders.
Original Primary Outcome:
Current Secondary Outcome: Determination of themes motivatiing subjects attitudes regarding the pursuit of whole genome sequencing and their interest in receipt of secondary results.
Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: March 13, 2010
Date Started: February 17, 2010
Date Completion:
Last Updated: April 21, 2017
Last Verified: April 5, 2017
