About Angelman Syndrome
AS Genotypes: UPD/ICD
An individual with UPD, or Uniparental Disomy, has two copies of chromosome 15 from their father, instead of one each from the father and mother; because the father’s side of this gene is silent, that means these people have not one but two silent alleles. In those with ICD or an Imprinting Center Defect, the mother’s chromosome 15 is blank, and the imprinting center copies the father’s chromosome 15—also, as with UPD, leaving the person with only silent paternal material.
These two genotypes are technically different, but functionally the same, which is why you’ll see them grouped together in AS literature. In contrast to AS deletions, where millions of base pairs of DNA on the maternal allele are missing, those with UPD/ICD are not missing a single base pair of DNA—which generally makes their features broadly less severe. (In addition, some ICD are also Mosaic. Generally, UPD cases are not.)
FAST puts enormous resources behind fighting for the inclusion of UPD/ICD in both research as well as clinical trials. All the pharma companies in our space have stated that they want to have the most consistent group for the earliest phases of clinical trials (Phase 1/2), and in many cases they want the most severely affected to start with. That is generally considered deletions (plus, in the case of certain trials, mutations). Once they can show safety (Phase 1) and early efficacy (Phase 2)—which are generally run together in trials as a Phase 1/2—then they will likely add a cohort of other genotypes.
You can read more about the future of UPD/ICD inclusion in trials in this Q&A with FAST Chief Science Officer Allyson Berent.
Connect with other AS UPD/ICD families by writing to us here: email@example.com