Gene Discovery Core, The Manton Center

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.

Study Overview

• Status: Recruiting
• Conditions: Rare Disorders; Orphan Diseases; Undiagnosed Conditions

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 Type: Observational
• Enrollment (Estimated): 10000

Contacts and Locations

• Study Contact: Name: Katie Anderson, MS, CGC; Phone Number: 617-919-4287; Email: gdc@childrens.harvard.edu
• Study Contact Backup: Name: Casie Genetti, MS, CGC; Phone Number: 617-919-2169; Email: gdc@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Casie A Genetti, MS, CGC; Phone Number: 617-919-3378; Email: gdc@childrens.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	1-10 years

Collaborators and Investigators

• Sponsor: Boston Children's Hospital

Publications and helpful links

Helpful Links

• The Manton Center website

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: January 4, 2016
• First Submitted That Met QC Criteria: April 14, 2016
• First Posted (Estimated): April 19, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Rare; Orphan Disease; Undiagnosed; Genomic Sequencing
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Rare Diseases
• Other Study ID Numbers: 10-02-0053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: If a genetic etiology is found, individual results are reported back to families.