The Generative Brain

Preimplantation genetic testing (PGT) for PRNP variants, including exclusion PGT

PGT is done during in vitro fertilisation: cells from early embryos are tested and only embryos that did not inherit the familial PRNP variant are transferred, so that a child does not carry the variant. Direct PGT tests the embryo for the known family variant; exclusion PGT, also called non-disclosure PGD, uses linked markers to transfer only embryos that did not inherit the at-risk grandparent's chromosome copy, so an at-risk parent who does not want to learn their own status never does. The first published use for a genetic prion disease was a 2014 US case report concerning the F198S variant that causes GSS. Israel publicly funds PGT for up to two healthy children and offers exclusion PGT to first- and second-degree relatives of people with genetic CJD. In the UK the fertility regulator's PGT-M list appears to include CJD and Gerstmann-Straussler disease as approved conditions, though this was seen only in search excerpts. Information only, not medical, reproductive or legal advice.

Key facts

  • A 2014 JAMA Neurology case report from Duke University, the Reproductive Genetics Institute in Chicago, the Institute for Human Reproduction in Chicago, the University of Chicago and the UCSF Memory and Aging Center describes itself as the first use of PGD with IVF to prevent a genetic prion disease, here GSS due to PRNP F198S.
  • The method described combined ICSI with sequential polar body testing and day-3 embryo biopsy, using linked markers to guard against failed amplification and allele dropout; the report names non-disclosure PGD as an available protocol for people who do not want to learn their own genotype.
  • The 2014 authors concluded that clinicians should discuss PGD as an option with people genetically predisposed to prion disease, and suggested that its availability may affect decisions about predictive testing.
  • The 2026 Israeli practice framework separates direct PGT, which tests embryos for a known family variant, from exclusion PGT, which selects embryos that did not inherit the at-risk allele from the affected grandparent while the parent's own status stays unknown.
  • In Israel exclusion PGT is offered at tertiary centres to first- and second-degree relatives of people with genetic CJD, and PGT in general is publicly funded for up to two healthy children.
  • The Israeli panel's Recommendation 5 is that PGT and prenatal genetic testing for genetic CJD be considered case by case; it notes prenatal diagnosis by chorionic villus sampling or amniocentesis is possible but that ending a pregnancy after a positive result raises major ethical issues.
  • A 2013 UCSF ethics review gives the US cost of PGD as typically 10,000 to 15,000 US dollars and usually not covered by insurance, and raises concerns about stigma for those who cannot or do not want to use it.
  • A 2022 review led from Case Western Reserve University lists PGD with IVF and in utero testing as the two main routes for carriers to have biological children without the variant, and states that PGD can be done without the parent learning their own status.
  • The UK HFEA keeps a list of conditions approved for PGT-M; search excerpts of that list show Creutzfeldt-Jakob disease (OMIM 123400) and Gerstmann-Straussler disease (OMIM 137440) as approved; the regulator says unlisted conditions can be applied for by licensed clinics.
  • A 2025 study of D178N and E200K families found transmission to offspring above the expected 50 percent, and its authors say embryo selection strategies in PGD programmes may need review and that reproductive outcomes in PGD programmes should be studied.
  • Hospital Clinic de Barcelona's PICOGEN programme tells relatives in genetic prion disease families about inheritance, carrier testing and options for preventing transmission to their children, without naming PGT.

Timeline

  1. 1990First live birth after PGD (for cystic fibrosis), cited as background in the 2013 ethics review.
  2. 2013UCSF ethics review describing PGD for genetic prion disease, with US cost estimate, published online.
  3. 2014First published case of PGD with IVF for a genetic prion disease (PRNP F198S) appears in JAMA Neurology with an accompanying comment.
  4. 2022Review on genetic aspects of human prion diseases lists PGD among reproductive options for carriers.
  5. 2025Transmission ratio distortion study for D178N and E200K families published, raising questions for PGD programmes.
  6. 2026Israeli practice framework published, describing direct and exclusion PGT and public funding.
  7. 2026Date of the current HFEA full approved PGT-M condition list file (contents not opened).
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