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Gene Discovery Core, The Manton Center

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02743845
Recruitment Status : Recruiting
First Posted : April 19, 2016
Last Update Posted : June 2, 2023
Information provided by (Responsible Party):
Alan H. Beggs, Boston Children's Hospital

Brief Summary:

The Gene Discovery Core at The Manton Center for Orphan Disease Research based at Boston Children's Hospital studies families with rare, poorly understood or undiagnosed, but suspected genetic conditions. The primary goal of the research is to better understand the genes and proteins (gene products) involved in rare diseases. The researchers hope that our studies will allow for improved diagnosis and treatment of individuals with rare disease in the future. Individuals with any rare/undiagnosed condition are eligible to enroll.

Enrollment includes:

  • Providing DNA and tissue samples (when available)
  • Access to participants' medical records
  • Access to genomic data (when available)

Samples are used for genetic analysis (primarily exome and genome sequencing or reanalysis) to identify the genetic cause for the individual's illness. Individual research results are returned to families through their health care provider after confirmation in a clinical lab. If a cause is identified, that can be reported back to the family through their health care provider and the study's genetic counselor. When possible, the investigators also collect samples from parents and full-siblings as well as any other affected family members.

Condition or disease
Undiagnosed Conditions Rare Disorders Orphan Diseases

Detailed Description:

Participants may be recruited from Boston Children's Hospital (BCH) or from off-site collaborators/healthcare providers who determine a participant as eligible. Participants may also contact the lab directly after hearing about the research through other individuals, recruitment materials, or the study's website ( After consenting to participation, individuals with rare disorders with a suspected, but unknown/poorly understood genetic basis, and their family members are asked to participate in the study by providing 1) relevant medical information/records and family history 2) a blood/saliva/DNA/RNA sample, and 3) preexisting tissue samples (including preexisting prenatal samples) that is no longer needed for clinical care (if available) or future tissue sample specifically for research purposes.

The medical records and family history allow the investigators to gain a better understanding of the specific disease symptoms seen in an individual or family. The blood/saliva sample is used to obtain DNA and/or RNA, and/or other biochemical which can then be analyzed for identifying the genetic bases of disease pathophysiology using various approaches including genomic sequencing. Tissue samples obtained from individual participants are employed to better understand gene expression and protein interactions through investigations such as (but not limited to) immunohistochemical and microarray analysis.

This study project will be ongoing for an indefinite period of time, and participation is continuous unless an individual requests to be removed from the study. Participants can request to withdraw at any time. Active participation primarily takes place at the time of enrollment and on a case-by-case basis thereafter for providing clinical updates and/or additional samples. Risks include those associated with routine blood draws/saliva sample collections and emotional distress associated with genetic and/or medical research. Risks are minimized as much as possible by an open consent process and privacy/confidentiality safeguards, including a certificate of confidentiality from the NIH and the use of de-identified, numerical codes to refer to participants with collaborators. Although there are no immediate, direct benefits to participants, the possible benefits of this study include the development of new diagnostic tests and more detailed prognostic information for participants and their families. In addition, this study may lead to a better understanding of the pathophysiology of these conditions, leading to the development of treatments and cures for both rare and more common disorders in the future.

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Study Type : Observational
Estimated Enrollment : 10000 participants
Observational Model: Family-Based
Time Perspective: Prospective
Study Start Date : February 2010
Estimated Primary Completion Date : December 2030
Estimated Study Completion Date : December 2030

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Identification of rare or novel disease-causing genetic variants for a participant's disorder [ Time Frame: 1-10 years ]
    Functional analysis, including animal modeling and cell line assays, will be performed for novel candidate genes. When a molecular diagnosis is identified for a family, this is reported back through a designated health care provider.

  2. Characterization of clinical features of novel and rare disorders using Human Phenotype Ontology (HPO) terms [ Time Frame: 1-10 years ]
    As known and new disease genes are identified the resulting genotypes are correlated with subject phenotypes.

Biospecimen Retention:   Samples With DNA
DNA RNA Tissue Samples Cell lines

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals with a rare or unknown but presumed genetic diagnosis and their family members.

Inclusion Criteria:

  • Having a known or uncertain rare diagnosis which may have a poorly understood genetic component and/or be a relative to a person with such a diagnosis

Exclusion Criteria:

  • Not having such a diagnosis and/or not being related to such an individual

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02743845

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Contact: Jill Madden, PhD,MS, CGC 617-919-4287

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United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Casie A Genetti, MS, CGC    617-919-3378   
Sponsors and Collaborators
Boston Children's Hospital
Additional Information:
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Responsible Party: Alan H. Beggs, Professor of Pediatrics, Boston Children's Hospital Identifier: NCT02743845    
Other Study ID Numbers: 10-02-0053
First Posted: April 19, 2016    Key Record Dates
Last Update Posted: June 2, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: If a genetic etiology is found, individual results are reported back to families.
Keywords provided by Alan H. Beggs, Boston Children's Hospital:
Orphan Disease
Genomic Sequencing
Additional relevant MeSH terms:
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Rare Diseases
Disease Attributes
Pathologic Processes