ASK THE EXPERT
Our new monthly addition to the newsletter, an Ask the Expert Q&A.
Question: Has FOXP1 research evolved enough to illustrate differences in symptoms specific to the genetic diagnosis of deletion, frameshift mutation or pathogenic mutation? Stated another way, is it possible looking at the genetic report to anticipate specific symptoms?
Answer: We asked the SAB and developed the following response from 3 of our SAB advisors (Drs. Eichler, Schenck, and Rappold). In short, this is a good but difficult question to fully address. The short answer is we do not yet have a full understanding of mutations and outcomes, but it is something that many of us are working towards. There are 2 or 3 key issues facing scientists and our community:
1. Scientists need to study lots of patients with standardized phenotyping to have the statistical power to be able to link different mutations with different outcomes. These links are sometimes referred to as genotype-phenotype relationships. It could take 100s of individuals with carefully collected data to understand these possible relationships.
2. But, even beyond the FOXP1 gene change, we need to understand other possible genome variations that could have exacerbating or mitigating effects on how an individual’s FOXP1 change affects them. These variations could be mutations in other genes, different “metagenomic” effects that affect how other genes are expressed even if not mutated, and many other phenomena.
3. Finally, there are random events in every individual’s life that affect how the brain and other parts of the body develop and are “wired up.” These can be extremely subtle and difficult to study, including environmental effects and even random events at the molecular level for normal proteins and systems – but they can be very influential on the final outcome/presentation.
Especially for issues #1 and #2, this is why it is so important to continue participating in research studies. As Dr. Eichler put it, “It is important to … not stop the genetic odyssey at simply an exome or microarray result -- ie [it’s important to also be] building a biobank of material for subsequent DNA, RNA, methylation etc. analyses.” There are at least 2 ways you and your family can contribute to research:
1. Participate in the Foundation’s RareX data collection program and potentially other research efforts too. These data will help build our understanding of FOXP1 syndrome, especially for individuals at different developmental stages (including following individuals over time to see how they develop – the natural history study)
2. Provide samples for research (cells, genetic material, scans, etc.). Some of this can be biobanked in freezers, to use for possible future analyses as new insights and techniques emerge. This is something the International FOXP1 Foundation is actively investigating.
