Can You Join FFI Research Without Learning Your PRNP Status?

Yes, it is sometimes possible to participate in fatal familial insomnia (FFI) and prion disease research without learning whether you carry a genetic variant. However, this depends entirely on the design of the specific study.

Some research initiatives, including specialized registries and certain proposed presymptomatic prevention trials, are designed to allow at-risk family members to participate while keeping their genetic status hidden from them (a “genotype-blinded” or “nondisclosure” approach) ^[1][2]. Because not every trial can accommodate this preference, you must carefully discuss your desire not to know your status with the research team before enrolling ^[3][4].

Important Note: Participating in research is completely voluntary and is different from receiving clinical care. An experimental study may offer no guaranteed personal benefit, and participating or declining will not affect your regular medical care. Research genetic testing is also different from clinical testing, and any research findings typically require a separate, clinically validated test before they are used to make medical decisions.

How Genotype-Blinded Studies Work

In a genotype-blinded study, researchers may test your DNA to determine if you carry the specific pathogenic PRNP variant identified in your family, but they will not reveal the results to you. It is important to note that not all PRNP variants cause FFI, so the study will look specifically for your family’s variant.

As an example of how this can work, a proposed prevention trial design for FFI explored allowing individuals who did not want to know their status to participate. In that proposed design, genetic carriers would receive an experimental treatment while non-carriers would receive a placebo, and the clinical examiners evaluating the participants’ health would remain blinded to their genetic status ^[1][2]. Other studies may use different designs, such as testing only carriers or using non-carriers as controls, which affects how blinding is maintained.

In observational research or registries, researchers might follow both mutation carriers and non-carriers over time. They gather baseline data through repeated clinical visits, brain MRI, spinal fluid collection, and sleep studies, without returning individual genetic results to the participants ^[5][3]. Keep in mind that study procedures like lumbar punctures or MRIs carry their own physical burdens and risks, which should be detailed in the study’s informed consent document. You always have the right to ask about the risks of individual procedures and whether they are optional.

Discussing Your Preference Not to Know

If you prefer not to learn your genetic status, this is an option you should request. The study team should explicitly explain whether this is possible and document your preference during the informed consent process ^[3][6].

Choosing not to know is a deeply personal decision, and it is not always psychologically neutral. Research involving some families with inherited prion disease shows that high levels of anxiety can occur among both tested and untested individuals, and non-carriers may experience survivor’s guilt or ongoing family distress ^[7]. Participating in research without knowing your status can bring up complex emotions, so it is highly recommended to seek genetic counseling (guidance from a trained healthcare professional) to help navigate this choice ^[7][6].

A counselor can also explain penetrance (the likelihood that a person with the variant will develop the disease); while penetrance can vary widely among different PRNP variants, some FFI-associated variants are highly penetrant, meaning the disease is very likely to occur if the variant is present ^[8][9].

Safeguards and Risks of Accidental Disclosure

When participating in research without knowing your status, safeguards can reduce but cannot entirely eliminate the risk that your genetic status could be accidentally revealed or inferred.

Longitudinal research often involves repeated clinical visits and tests ^[5]. Differences in how study coordinators communicate with you, the specific procedures you undergo, or the side effects you experience from an intervention could provide clues about your underlying status ^[5].

Additionally, if your research results enter your standard electronic health record, your treating doctors or family members might unintentionally see them ^[5][10]. You should ask the research team exactly what privacy safeguards they use—such as keeping research records coded and entirely separate from clinical records, limiting who holds the key to the code, and whether a Certificate of Confidentiality or other legal privacy protection applies.

Future Use of Your Samples

When you join a study, biological samples (like blood or spinal fluid) might be stored in a biobank (a repository that stores biological samples for use in research) for future use. Future researchers might perform whole-genome sequencing or look at your PRNP gene, and policies on returning these future results vary by study ^[11][12].

While you can often ask to opt out of receiving optional genetic results from future research, you must check the specific limits outlined in your consent form ^[12]. Furthermore, once your samples or data have been de-identified, shared with outside researchers, or incorporated into aggregate analyses, it may no longer be possible to withdraw them ^[13][14].