Intellectual DisabilitiesNCT01087320
Genome Medical Sequencing for Gene Discovery
An observational study of Intellectual Disabilities and Congenital Anomaly, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial 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 "genome sequencing" to learn which gene or genes cause these conditions. Read more about this study
- Who is it for?
- Ages 4 weeks to 99 years
- Conditions the study is for
- Intellectual Disabilities, Congenital Anomaly, Rare Disorders
- How many people
- 2,000 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Feb 2010to not given
- 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 4 weeks to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients or family probands with genetic cause of disorders that are intractable or difficult to identify with existing technique.
Who may be able to join
- An individual who is affected with a disorder under study and is older than 4 weeks. Our initial list of exemplar disorders has been discontinued; these disorders were examples of those which meet the general attributes for inclusion in this protocol. As stated above, individuals with disorders we choose to investigate under this protocol will generally represent simplex cases with rare phenotypes whose molecular etiology is unknown. For individuals less than 2 years of age, per NIHCC policy we do not generally admit them and limit our evaluations to outpatient evaluations of generally healthy infants and toddlers. In rare instances, we may accept DNA from deceased individuals, in accordance with Policy 400.
- Family members of an affected individual where that family member (often a parent) is potentially informative or useful for linkage or other bioinformatic analyses of genetic variants may be enrolled. Probands who are minors or decisionally impaired adults are eligible if they have a parent or legal guardian who has authority to sign a consent form on their behalf.
Who cannot join
- Probands who are adults and decisionally impaired are ineligible if they do not have a legal guardian who has authority to sign a consent form on their behalf.
- Subjects who have known, significant affective or psychiatric disorders that, in the judgment of the team, may impair their ability to understand and appropriately use complex medical and genetic information will be considered decisionally-impaired and will be ineligible unless they have appointed (or, in the case of minor children, are in the custody of) an appropriate surrogate decision-maker.
- In addition, guardianship for cognitively impaired adult probands must be legally established and proof of guardianship must be supplied prior to that family s enrollment.
- We request the ability to use this protocol for multiple genetic disorders, without specifically delineating them a priori. We believe this approach to be appropriate because for nearly all inherited disorders, the risks and benefits of GSMS do not substantively differ. This concept was validated by our now-closed protocol 94-HG-0193, which was a broad-based protocol for heritable congenital anomaly disorders, many of which do not fall neatly into a specific diagnostic classification.
- As mentioned, we may request permission to retain some information about prospective participants who, at the time of their inquiry, may not be eligible for the study but who could become eligible in the future. As these participants will not be signing a consent form, we propose to NOT count these participants in our Inclusion Enrollment Reports but will provide the IRB with a tally of retained records at each Continuing Review.
- Consent documents for this protocol are available in English and Spanish. In rare instances, we may enroll participants who speak other languages using the NIH Short Written Consent Form Translation.
- We will not enroll pregnant women, except as outlined in the section above.
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
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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 "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.
Read more
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 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 be required to proceed with some of our gene sequencing studies.
- Clinical photographs to document certain aspects of the disorder.
- Blood, saliva, and skin biopsy samples, or other tissue samples, as required by the study doctors.
- Genetic testing, as decided by the researchers. However, most participants in this study can expect to undergo genome sequencing, which is a technique to study all of a person's genes.
- Participants will have choices about what kinds of results from genome sequencing they wish to learn.
- After the tests have been completed and the results of the genetic studies are known, participants may be offered a return visit to the National Institutes of Health to learn these results, or the results may be returned by telephone or by a participant's home provider.
Read the detailed description
We aim to use genome scale medical sequencing (GSMS, to include exome and genome sequencing as appropriate) 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 GSMS 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 GSMS process (what we refer to as "secondary variants"). Participants will be offered a return visit to NIH to learn these results.
Sequence data generated at the NIH Intramural Sequencing Center (NISC) will be screened by staff in the Biesecker laboratory for sequence variants that conform to the hypothesized inheritance pattern. All sequence variants deemed clinically relevant will be validated in a CLIA-certified laboratory and the results returned to that participant. This protocol is being designed in a way that will provide the long-term potential for pursuing many different clinical projects.
- Keywords
- Rare Disorders, Natural History, Genome Sequencing, Genetic Disorders, Congenital Disorders, Inherited Diseases
- Medical subject headings
- Intellectual Disability, Congenital Abnormalities, Genetic Diseases, Inborn, Congenital, Hereditary, and Neonatal Diseases and Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Genetic Disorders | Patients or family probands with genetic cause of disorders that are intractable or difficult to identify with existing technique. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analyze GSMS results for rare disorders for which genetic causes are known but not fully described
We aim to sequence penetrant cases to study the molecular variations of rare genetic disorders, to better predict pathogenicity and identify new causative variants.
Measured: Ongoing
Molecular etiology of rare diseases
Identify the genetic cause of disorders that are intractable or difficult to identify with existing techniques, for example, disorders due to new mutations with poor reproductive fitness, through exome or genome sequencing.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2010 (estimated)
- Study start18 Feb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Intellectual DisabilitiesStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Leslie G Biesecker, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01087320
- Sponsor's protocol ID
- 100065
- Other IDs
- 10-HG-0065
- Status last verified
- 28 Oct 2026
- First submitted
- 13 Mar 2010
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Evans JP, Green RC. Direct to consumer genetic testing: Avoiding a culture war. Genet Med. 2009 Aug;11(8):568-9. doi: 10.1097/GIM.0b013e3181afbaed. No abstract available.
PubMed 19606051Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet. 2008;9:387-402. doi: 10.1146/annurev.genom.9.081307.164359.
PubMed 18576944Marteau TM, Dormandy E, Michie S. A measure of informed choice. Health Expect. 2001 Jun;4(2):99-108. doi: 10.1046/j.1369-6513.2001.00140.x.
PubMed 11359540
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genome Medical Sequencing for Gene Discovery
- ClinicalTrials.gov ID
- NCT01087320
- Acronym / sponsor ID
- 100065
- Keywords
- Rare Disorders, Natural History, Genome Sequencing, Genetic Disorders, Congenital Disorders, Inherited Diseases
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 18 Feb 2010 (actual)
- First posted
- 16 Mar 2010 (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.
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 "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 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 be required to proceed with some of our gene sequencing studies.
- Clinical photographs to document certain aspects of the disorder.
- Blood, saliva, and skin biopsy samples, or other tissue samples, as required by the study doctors.
- Genetic testing, as decided by the researchers. However, most participants in this study can expect to undergo genome sequencing, which is a technique to study all of a person's genes.
- Participants will have choices about what kinds of results from genome sequencing they wish to learn.
- After the tests have been completed and the results of the genetic studies are known, participants may be offered a return visit to the National Institutes of Health to learn these results, or the results may be returned by telephone or by a participant's home provider.
Detailed description
We aim to use genome scale medical sequencing (GSMS, to include exome and genome sequencing as appropriate) 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 GSMS 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 GSMS process (what we refer to as "secondary variants"). Participants will be offered a return visit to NIH to learn these results.
Sequence data generated at the NIH Intramural Sequencing Center (NISC) will be screened by staff in the Biesecker laboratory for sequence variants that conform to the hypothesized inheritance pattern. All sequence variants deemed clinically relevant will be validated in a CLIA-certified laboratory and the results returned to that participant. This protocol is being designed in a way that will provide the long-term potential for pursuing many different clinical projects.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Genetic Disorders | – | –Patients or family probands with genetic cause of disorders that are intractable or difficult to identify with existing technique. |
Who may qualify
- Ages
- 4 weeks to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients or family probands with genetic cause of disorders that are intractable or difficult to identify with existing technique.
Key inclusion criteria (2 listed)
- An individual who is affected with a disorder under study and is older than 4 weeks. Our initial list of exemplar disorders has been discontinued; these disorders were examples of those which meet the general attributes for inclusion in this protocol. As stated above, individuals with disorders we choose to investigate under this protocol will generally represent simplex cases with rare phenotypes whose molecular etiology is unknown. For individuals less than 2 years of age, per NIHCC policy we do not generally admit them and limit our evaluations to outpatient evaluations of generally healthy infants and toddlers. In rare instances, we may accept DNA from deceased individuals, in accordance with Policy 400.
- Family members of an affected individual where that family member (often a parent) is potentially informative or useful for linkage or other bioinformatic analyses of genetic variants may be enrolled. Probands who are minors or decisionally impaired adults are eligible if they have a parent or legal guardian who has authority to sign a consent form on their behalf.
Key exclusion criteria (7 listed)
- Probands who are adults and decisionally impaired are ineligible if they do not have a legal guardian who has authority to sign a consent form on their behalf.
- Subjects who have known, significant affective or psychiatric disorders that, in the judgment of the team, may impair their ability to understand and appropriately use complex medical and genetic information will be considered decisionally-impaired and will be ineligible unless they have appointed (or, in the case of minor children, are in the custody of) an appropriate surrogate decision-maker.
- In addition, guardianship for cognitively impaired adult probands must be legally established and proof of guardianship must be supplied prior to that family s enrollment.
- We request the ability to use this protocol for multiple genetic disorders, without specifically delineating them a priori. We believe this approach to be appropriate because for nearly all inherited disorders, the risks and benefits of GSMS do not substantively differ. This concept was validated by our now-closed protocol 94-HG-0193, which was a broad-based protocol for heritable congenital anomaly disorders, many of which do not fall neatly into a specific diagnostic classification.
- As mentioned, we may request permission to retain some information about prospective participants who, at the time of their inquiry, may not be eligible for the study but who could become eligible in the future. As these participants will not be signing a consent form, we propose to NOT count these participants in our Inclusion Enrollment Reports but will provide the IRB with a tally of retained records at each Continuing Review.
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
Analyze GSMS results for rare disorders for which genetic causes are known but not fully described
Time frame: Ongoing
We aim to sequence penetrant cases to study the molecular variations of rare genetic disorders, to better predict pathogenicity and identify new causative variants.
Molecular etiology of rare diseases
Time frame: Ongoing
Identify the genetic cause of disorders that are intractable or difficult to identify with existing techniques, for example, disorders due to new mutations with poor reproductive fitness, through exome or genome sequencing.
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 5 Nov 2026.
- Background: PubMed 19606051Evans JP, Green RC. Direct to consumer genetic testing: Avoiding a culture war. Genet Med. 2009 Aug;11(8):568-9. doi: 10.1097/GIM.0b013e3181afbaed. No abstract available.
- Background: PubMed 18576944Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet. 2008;9:387-402. doi: 10.1146/annurev.genom.9.081307.164359.
- Background: PubMed 11359540Marteau TM, Dormandy E, Michie S. A measure of informed choice. Health Expect. 2001 Jun;4(2):99-108. doi: 10.1046/j.1369-6513.2001.00140.x.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Leslie G Biesecker, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
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 Intellectual Disabilities and Congenital Anomaly, run by National Human Genome Research Institute (NHGRI) 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 2 inclusion and 7 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 5 Nov 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 Julie C Sapp ((301) 435-2832, sappj@mail.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analyze GSMS results for rare disorders for which genetic causes are known but not fully described (time frame: Ongoing). 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?
On the ClinicalTrials.gov record for NCT01087320, which also lists 3 linked publications.
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 5 Nov 2026.