Using genome sequencing to discover genetic causes of rare disorders

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This observational study aims to utilize genome sequencing technology to identify the genetic causes of rare inherited diseases that currently lack known genetic explanations. Researchers will recruit affected individuals and their parents to undergo genome scale medical sequencing, which includes exome and whole genome sequencing. The study seeks to uncover causative genetic variants for these disorders and develop best practices for the medical and counseling challenges associated with genome sequencing. Participants will have the option to learn about clinically relevant results related to their conditions.

Why it matters

Who can join: the full rules

* INCLUSION CRITERIA:

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.

EXCLUSION INCLUSION:

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.

Where it's running

• National Institutes of Health Clinical Center
  Bethesda, Maryland, United States Recruiting

Study contacts

• Principal investigator: Leslie G Biesecker, M.D. — National Human Genome Research Institute (NHGRI)
• Study coordinator: Julie C Sapp
• Email: sappj@mail.nih.gov
• Phone: (301) 435-2832

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.