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 chromosome 15 are missing, those with UPD or ICD may be missing no DNA (in the case of methylation ICD) or only a very small amount of DNA (in the case of ICD deletion), which generally makes their features less severe. (In addition, some ICD are also Mosaic. Generally, UPD cases are not.)

• Go here to dive into UPD, including information on chances for future children, and connect with other AS UPD families.

• Go here to dive into ICD, including information on chances for future children, and connect with other AS ICD families.

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.

Still have questions?

If you are wondering about your specific chance to have a child with a genetic variant that causes AS, it is very important to consult a genetics professional like a genetic counselor or geneticist. The chance varies depending upon the test results of the person living with AS and the testing that was performed on the parent(s). The information provided here may be helpful but it is not specific to your family and is not meant to replace genetic counseling.