What are genes?
Genes are the biological templates the body uses to make the structural proteins and enzymes needed to build and maintain tissues and organs. They are made up of strands of genetic code, denoted by the letters G, C, T and A. Humans have about 30,000 genes bundled into 46 chromosomes all coiled up in the nucleus of nearly every cell in the body.
What are G, C, T and A?
The letters of the genetic code refer to the molecules guanine (G), cytosine (C), thymine (T) and adenine (A). In DNA, these molecules pair up: G with C and T with A. These “base pairs” become the rungs of the familiar DNA double helix. Each of us inherits about 60 new mutations from our parents, so actually having a mutation is extremely common! Unfortunately, in the case of our GRIN children, the pinpoint mutation of only one nucleotide out of 6 billion was in such a critical place that it causes a disease.
About GRIN Genes
The NMDA Receptor responsible for sending messages between nerve cells and has a critical role with learning and memory functions in the brain.
The genetic information that is required for this receptor’s functionality is stored across 7 genes named GRIN (GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, and GRIN3B). A single change at any of these genes’ critical sections causes the GRIN disorders.
When such a change happens in a gene, this is referred to as a variation or mutation.
There are several hundred people who known to have a GRIN disorder (worldwide), almost every one has a different, unique, change and manifests subset of known symptoms which are related to the dysfunctionality of the NMDA Receptor.
The terminology we often use
- Gain of Function (GOF) – When there is over-activity of the Receptor
- Lost of Function (LOF) – When there is under-activity of the Receptor
- Missense Mutation – When a single nucleotide is changed, and as a result a different protein is produced (more)
- Deletion Mutation – When the entire or part of the gene is missing (more)
Why and how does a mutation happen?
There are several causes for the GRIN mutations, the most common is called de novo, which means it happens spontaneously at the early stages of pregnancy.
Every human being has about 60 such mutations, since every human has more than 6 billion nucleotides (think about it as a book composed of 6 billion characters) the probability a mutation will happen in one of the critical area of the GRIN genes is very low.
A much less common cause for a GRIN disorder is an inherent mutation from one of the parents.
Currently, there are less than 500 known people living with GRIN disorders, worldwide. As Whole Exome Sequencing (WES test) becomes more accessible, we will see the number of individuals diagnosed with a GRIN disorder increase.
What should I expect to happen to my beloved? What are the possible symptoms?
Most of the patients with GRIN disorders will have a normal life span. The main influence of GRIN genes is the brain, therefore the disorders do not involve other organs.
With your loved ones’ genetic test (WES) results, you should contact (email) one of the centers that perform functional testing, which will most likely provide you with a detailed projection for your children’s specific mutation.
You can also search this list of known variants if the exact same variant has been documented.
The most common symptoms are: Global developmental delays, Epilepsy (seizures), Hypotonia (low muscle tone), Intellectual disability, Nonverbal (or delayed speech) and more.
Is there a cure?
Currently, there is no existing cure for GRIN Disorders. This is the reason why the foundation has been formed.
The GDRF is dedicated to finding a cure for GRIN genes disorders.
What are the treatment options?
Although there is currently no cure for GRIN Disorders, symptoms may be improved with various therapies. Please see the Families section for more information.
What are the major differences between the GRIN genes?
Actually, there are no major differences.
A child with a GRIN2D variant may have the exact same symptoms and future therapies as a child with a GRIN2B variant, while two children with two different GRIN1 variants may be completely distinct both by symptoms and therapies.
Be sure to join the GRIN parent support groups, see links at the Families section.
Although not doctors, other parents are often one of the best sources of information and support.