Functional Analysis

What to do now that I have a GRIN diagnosis?

Usually, you will receive your GRIN diagnosis from a geneticist. Unfortunately, geneticists in principle only diagnose an illness but do not provide treatment. Your child’s pediatrician or pediatric neurologist should consequently be the one guiding your next steps. Unfortunately, however, GRIN gene mutations have only been recently described and there is not enough widespread knowledge about these group of diseases. Your doctor may consequently lack the knowledge to offer treatment and therapy options for your child. As the European Patient Organization for GRIN disorders, we are always happy to provide you with information on treatment and therapy options for your child and, through our extensive global network, to bring your child’s doctors in contact with GRIN researchers and GRIN specialists from around the world.

Following your diagnosis, the first steps would be to do a FUNCTIONAL ANLYSIS to determine the changes caused by your child’s GRIN mutation. Unfortunately, a functional analysis is usually not included in the genetic report containing the GRIN diagnosis. It is however paramount to obtain functional information before considering treatment options for your child.

Right now, there are two GRIN databases that contain functional analysis information for already tested known mutations.  Parents could ask their child’s neurologist or geneticist to check the child’s variant/mutation in any of these databases. It may however be that your child´s mutation is not listed in any database, and your neurologist/geneticists will not have more information for you without further testing of the mutation in the laboratory. 

Links for the databases: 

https://alf06.uab.es/grindb/home

https://grin-portal.broadinstitute.org/

Currently, there are over 4000 mutations cataloged in the different GRIN databases and this number keeps growing as research into the various mutations continues. The information in the database first explains if a specific mutation 1) has been found to be disease-causing (pathogenic) or not, or 2) whether it makes the neuroreceptor (made up of the 4 GRIN proteins) to have increased activity (Gain of Function or abbreviated, GoF) or decreased activity (Loss of Function or abbreviated, LoF). In the Gof and LoF section we will explain this at length. 

If your child’s mutation is not (yet) present in either one of these databases, it is important that you contact the two places where GRIN functional analyses are currently being conducted and that you sent them your child’s mutation and / or a copy of the genetic report. More centers will possibly be able to provide these analyses in the future, but at this stage, this is a slow process and very labour intensive. 

Barcelona GRIN team, in Barcelona Spain. Dr. Xavi Altafaj and Dr. Mireia Oliveia will help families determine the functional analysis. Please use the following email to contact them.

email: bcngrinteam@gmail.com

The Barcelona GRIN Team will contact you when the functional analysis is completed and will inform you whether the mutation results in LoF or GoF. In some cases, a mutation is defined as “complex”, meaning that the mutation exhibits elements of both LoF and GoF. See the GoF and LoF section for more information.

For Europe, CFERV, through the  Lipzig Unversity has database called the GRIN portal. www.grin-portal.broadinstitute.org

Please note that CFERV / the GRIN portal in most cases will not contact you when your child’s functional analysis is completed. New results are uploaded every three months and as a parent it is your own responsibility to check the database periodically for news on your child’s mutation.

*** If you want to try and find for your child’s mutation in either one of the database we have a tutorial under the Resources section called FUNCTIONAL ANALYSIS DIAGNOSTIC TUTORIAL that may help you.