Gene Discovery Core, The Manton Center


Lead Sponsor: Boston Children's Hospital

Source 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

Samples are used for genetic analysis (primarily exome and genome sequencing) 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 ( 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.

Overall Status Recruiting
Start Date February 2010
Completion Date December 2050
Primary Completion Date December 2050
Study Type Observational
Primary Outcome
Measure Time Frame
Identification of rare or novel disease-causing genetic variants for a participant's disorder 1-10 years
Characterization of clinical features of novel and rare disorders using Human Phenotype Ontology (HPO) terms 1-10 years
Enrollment 10000

Sampling Method: Non-Probability Sample


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

Gender: All

Minimum Age: N/A

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Last Name: Casie A Genetti, MS, CGC

Phone: 617-919-3378

Email: [email protected]

Facility: Status: Contact: Boston Children's Hospital Casie A Genetti, MS, CGC 617-919-3378 [email protected]
Location Countries

United States

Verification Date

August 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Boston Children's Hospital

Investigator Full Name: Pankaj Agrawal

Investigator Title: Assistant Professor of Pediatrics

Has Expanded Access No
Condition Browse
Patient Data Yes
Study Design Info

Observational Model: Family-Based

Time Perspective: Prospective