Parents

CFERV tests GRINGRIAGRIK, and GRID gene variants upon request.

 

FAQs

 

What is meant by GRIN, GRIA, GRIK, and GRID genetic variation?

Anytime a change happens in the DNA for a gene this is referred to as variation.  A variant is also called a mutation as these terms are used interchangeably.  Several types of gene variation are possible, all of which mean the genetic DNA sequence code was altered in some way, for example, via deletion, insertion, or duplication via chromosomal rearrangement. Additionally, single nucleotides (referred to as A,C, G, and T) in the DNA sequence may be altered, changing the readout of the gene sequence into a protein. Proteins are made up of amino acids. The sequence of the genetic code defines the sequence of amino acids in the protein.  If the variant in the genetic sequence results in a change in the amino acid in the protein, this is called a missense mutation.  Most of the genetic variants CFERV investigates are rare missense variants; however, there are other types of variants (indels, frameshift, nonsense, and duplication mutations) that we can also investigate depending upon the location of the mutation.

What causes GRIN, GRIA, GRIK, and GRID gene variations?

Mutations occur spontaneously at or soon after conception, but the reasons for these changes are largely unknown.  In most cases, the change is de novo, occurring spontaneously in the genetic code of the sperm or egg that formed the child. It is also possible that a parent may have the mutation and pass it on to their children as an inherited or transmitted mutation.

Who can get GRIN, GRIA, GRIK, and GRID gene variants? 

Any individual can be born with one of these mutations.

What are the symptoms of GRIN, GRIA, GRIK, or GRID gene variations?

The symptoms of glutamate receptor mutations vary from person to person, depending on the specific gene affected and the type and location of the variant within the gene. Phenotypes are highly varied, but common ones include epilepsy, global developmental delay, hypotonia, intellectual disability, non-verbal or delayed speech, and autism.  See our Database with links to published scientific and medical journal reports for more detailed information.

Is there a cure for GRIN, GRIA, GRIK, or GRID gene variations?

Currently, there is no cure for these gene variants, as these changes occur at the genetic level of an individual.  However, doctors, researchers, and clinical institutions are planning and implementing clinical trials that may reduce associated symptoms.

What are my treatment options? 

Though there is no cure, treatment may be done through a symptomatic approach. Physical, occupational, and speech therapies can help children manage symptoms and reach developmental milestones. Epilepsy may be treated by a specialist. Additionally, The Cure Foundation has funded a retrospective clinical study of the utility of NMDA receptor antagonists, including memantine (Namenda), dextromethorphan, and ketamine (Ketalar) in the treatment of patients with Glutamate Receptor Associated Disorders that likely arises from a de novo GRIN genetic mutation or rare GRIN variants. Patients, with GRIN mutations, regardless of epilepsy or treatment, are also needed and encouraged to participate. For more information, try our Treatment Options page and follow links from there.

How are GRIN, GRIA, GRIK, or GRID gene variations diagnosed?

Mutations are identified through a genetic blood test called Whole Exome Sequencing (WES), which examines an individual's whole genetic makeup. This is then compared to the genetic sequences of the parents to determine if the variant was inherited or de novo

What can I do to help?

If you wish to contribute to CFERV's mission to provide experimental data on the functional consequences of each mutation, please donate.  All donations directly support the evaluation of functional effects of new patient-derived genetic variants and the maintenance of the publicly accessible database for clinicians, scientists, and parents to obtain information about functional effects of genetic variants. 

Glossary:

Missense mutation: A mutation that changes an amino acid in a protein. Also called a nonsynonymous mutation.

Nonsense mutation: A mutation that changes an amino acid in a protein to a stop codon which ends synthesis of the protein at that location. These mutations shorten the length of the protein.

Substitution mutation:  This is when a nucleotide in the gene sequence is replaced by another nucleotide.  We refer to the nucleotides as A, C, G, and T (for adenosine, cytosine, guanine, and thymidine). 

Insertion mutation: This occurs when extra nucleotides are inserted into a place in the DNA in the gene.

Deletion mutation: This occurs when nucleotides are lost, or deleted from the DNA in the gene.

Frameshift mutation:  The genetic code is a series of three nucleotides in a row that tell the cell which amino acid to put into the protein at that location.  Insertion and deletion mutations can change the “reading frame” of the genetic code.  For example, by analogy, this sentence:  “Bob ran  one lap”.  If one of the letters is removed, “ie the second b” and the letters are still parsed in groups of three (as the genetic code does),  it will read “ Bor  ano nel  ap.”  And thus, the frameshift mutation  changes the meaning of the code.

Genetic Code:  A series of three DNA nucleotides (referred to as A, C, G, and T) that is read by the cellular machinery to make a sequence of amino acids that become a protein.  Proteins are also known as enzymes, receptors, and transporters to name some examples.  The GRINGRIAGRIK, and GRID genes encode receptor proteins that respond to the neurotransmitter L-glutamate. 

Amino Acid

Amino Acid Abbreviations

DNA Genetic Code

RNA Genetic Code

Alanine

Ala

A

GCT GCC GCA GCG

GCU GCC GCA GCG

Arginine

Arg

R

CGT CGC CGA CGG AGA AGG

CGU CGC CGA CGG AGA AGG

Asparagine

Asn

N

AAT AAC

AAU AAC

Aspartate

Asp

D

GAT GAC

GAU GAC

Cysteine

Cys

C

TGT TGC

UGU UGC

Glutamate

Glu

E

GAA GAG

GAA GAG

Glutamine

Gln

Q

CAA CAG

CAA CAG

Glycine

Gly

G

GGT GGC GGA GGG

GGU GGC GGA GGG

Histidine

His

H

CAT CAC

CAU CAC

Isoleucine

Ile

I

ATT ATC ATA

AUU AUC AUA

Leucine

Leu

L

TTA TTG CTT CTC CTA CTG

UUA UUG CUU CUC CUA CUG

Lysine

Lys

K

AAA AAG

AAA AAG

Methionine

Met

M

ATG

AUG

Phenylalanine

Phe

F

TTT TTC

UUU UUC

Proline

Pro

P

CCT CCC CCA CCG

CCU CCC CCA CCG

Serine

Ser

S

TCT TCC TCA TCG AGT AGC

UCU UCC UCA UCG AGU AGC

Threonine

Thr

T

ACT ACC ACA ACG

ACU ACC ACA ACG

Tryptophan

Trp

W

TGG

UGG

Tyrosine

Tyr

Y

TAT TAC

UAU UAC

Valine

Val

V

GTT GTC GTA GTG

GUU GUC GUA GUG

Stop

Ter

X

TAG TAA TGA

UAG UAA UGA