Undiagnosed ConditionsNCT02743845
Gene Discovery Core, The Manton Center
An observational study of Undiagnosed Conditions and Rare Disorders, run by Boston Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Undiagnosed Conditions, Rare Disorders, Orphan Diseases
- How many people
- 10,000 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2010to Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals with a rare or unknown but presumed genetic diagnosis and their family members.
Who may be able to join
- 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
Who cannot join
- Not having such a diagnosis and/or not being related to such an individual
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Casie A Genetti, MS, CGC, 617-919-3378, gdc@childrens.harvard.edu
About this study
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:
Read more
- 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.
Read the 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 (www.childrenshospital.org/mantoncenter). 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.
- Conditions
- Undiagnosed Conditions, Rare Disorders, Orphan Diseases
- Keywords
- Rare, Undiagnosed, Orphan Disease, Genomic Sequencing
- Medical subject headings
- Rare Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of rare or novel disease-causing genetic variants for a participant's disorder
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.
Measured: 1-10 years
Characterization of clinical features of novel and rare disorders using Human Phenotype Ontology (HPO) terms
As known and new disease genes are identified the resulting genotypes are correlated with subject phenotypes.
Measured: 1-10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2016 (estimated)
- Study startFeb 2010
- Primary completionDec 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Undiagnosed ConditionsStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 10,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alan H. Beggs, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02743845
- Sponsor's protocol ID
- 10-02-0053
- Status last verified
- Mar 2026
- First submitted
- 4 Jan 2016
- Last updated
- 25 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: If a genetic etiology is found, individual results are reported back to families.
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gene Discovery Core, The Manton Center
- ClinicalTrials.gov ID
- NCT02743845
- Acronym / sponsor ID
- 10-02-0053
- Conditions
- Undiagnosed Conditions, Rare Disorders, Orphan Diseases
- Keywords
- Rare, Undiagnosed, Orphan Disease, Genomic Sequencing
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 10,000 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 19 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 (www.childrenshospital.org/mantoncenter). 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.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals with a rare or unknown but presumed genetic diagnosis and their family members.
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- Not having such a diagnosis and/or not being related to such an individual
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2026.
- The Manton Center websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. If a genetic etiology is found, individual results are reported back to families.
Related trials for Undiagnosed Conditions
RecruitingObservational study
Clinical and Genetic Evaluation of Individuals With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Genetic Disease
RecruitingObservational study
Vascular Disease Discovery Protocol
Vascular Dysfunction, Genetic Mutations
RecruitingObservational study
Genetic Analysis of Uncommon Disease Presentations in Non-US Populations
Undiagnosed Diseases, Rare Diseases
RecruitingObservational study
Human Biospecimen Procurement Protocol: Biorepository to Support Translational Research to Identify Disease Mechanism(s)
Undiagnosed Diseases, Cardiovascular Disease
Enrolling by invitationObservational study
The Mayo Clinic Rare and Undiagnosed Disease Hackathon
Undiagnosed Diseases, Genetic Diseases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Undiagnosed Conditions and Rare Disorders, run by Boston Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Katie Anderson, MS, CGC (617-919-4287, gdc@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of rare or novel disease-causing genetic variants for a participant's disorder (time frame: 1-10 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2026.