Are you interested in screening any gene variant?
If the gene causes epilepsy, intellectual disability, autism or another strong behavioral /neurological phenotype, then in principle the answer is yes. However, it also depends on a number of factors, such as what is the genetic evidence and does it concern a new gene or is it a variant of a previously described gene. Best thing to do is to send us an email
Can all gene variants be screened?
We can only screen missense and nonsense mutations in the coding DNA. Splice site and intronic mutations are not suitable for testing in PRiSM. The only technical limitation that we have for testing missense/nonsense mutations is the size of the gene. If the cDNA exceeds 4000 bp, our transfection/in utero electroporation efficiency becomes very low. Importantly, not all variants/genes give phenotypes in the assays we use. Under the tab ‘tested genes’ you can find a selection of the published genes and variants we already tested (but note that a substantial number of unpublished genes and variants are not included in that table).
Does it make sense to test a gene variant in the neuronal migration assay if no abnormalities in the patient MRI are observed?
Yes! Neuronal migration is an intricate process that requires optimal neuronal function. By overexpressing the mutated protein we exacerbate the effect of the mutation, and hence see delays in migration that are not observed in the patient. Moreover, since only a small minority of the cells is expressing the mutated gene, they have to compete with normal functioning cells. This will further exacerbate the effect of the mutation. Finally, we observe quite often that neuronal migration is only delayed, not halted. When the brains are examined at a later time point in development, the migration deficit may no longer be observed.
What are the costs?
At this point, we consider testing genen variants in PRiSM as a research collaboration. That means that the ultimate goal is to publish our findings in a peer reviewed journal. We do not charge any fees for such a collaboration. If the testing has a strong diagnostic focus and is less interesting from a scientific point of view, we request a cDNA clone, or we request to cover the costs of synthesizing the DNA (typically less than €2000).
What is the turnover time?
This largely depends on the number of genes we are currently working on, the priority we give it, and whether the DNA variant is already cloned, or still needs to be generated.
Is the PRiSM lab certified as a diagnostics lab?
We are currently not certified as a diagnostic lab. This will be implemented in the future when we have acquired more data.