Genome Medical Sequencing for Gene Discovery

NCT01087320 | Recruiting

• 2 other identifiers: 10006510-HG-0065
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Congenital Anomaly; Rare Disorders; Intellectual Disabilities

Keywords

Rare Disorders; Natural History; Genome Sequencing; Genetic Disorders; Congenital Disorders; Inherited Diseases

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Ongoing

Study Arms (1)

Genetic Disorders

Patients or family probands with genetic cause of disorders that are intractable or difficult to identify with existing technique.

Eligibility Criteria

• Age: 4 Weeks - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients or family probands with genetic cause of disorders that are intractable or difficult to identify with existing technique.

You may qualify if:

• Vital functions of the neonate will not be artificially maintained;
• The research will not terminate the heartbeat or respiration of the neonate;
• There will be no added risk to the neonate resulting from the research;
• The purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means; and
• The legally effective informed consent is obtained in accord with applicable regulations.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 19606051 BACKGROUND

• Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet. 2008;9:387-402. doi: 10.1146/annurev.genom.9.081307.164359.

  PMID: 18576944 BACKGROUND

• Marteau 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.

  PMID: 11359540 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Intellectual Disability; Congenital Abnormalities; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Leslie G Biesecker, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julie C Sapp

CONTACT

(301) 435-2832; sappj@mail.nih.gov

Leslie G Biesecker, M.D.

CONTACT

(301) 402-2041; lesb@mail.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2010
• First Posted: March 16, 2010
• Study Start: February 18, 2010
• Last Updated: May 5, 2026

Record last verified: 2026-05-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)