TRIO GENE MUTATION
What is TRIO Gene?
TRIO (Trio Rho Guanine Nucleotide Exchange Factor) is a Protein coding gene.
TRIO is located on the fifth chromosome, band 5p15.2 and codes for a protein that has many functions. These functions are important in fetal and neonatal brain development and later in life in sending messages between cells in the brain.
In very rare cases, people can be born with mutations in the TRIO gene. You or your child may have been told that you have a TRIO gene mutation. Sometimes this can occur in other family members as well. Depending on the type of mutation and exactly where the mutation is located on the DNA, this can cause different conditions.
A mutation on the TRIO Gene can be found with Genetic Testing. This tiny genetic difference has wide-reaching implications for a person’s physical, cognitive, and emotional well-being.
One important aspect of TRIO, is that this gene controls the growth and migration of neurons in the brain. Individuals with mutations in a gene TRIO may have a range of conditions, including varying degrees of intellectual disability and anomalous head size. The expression of those traits depends on where in the gene the mutation lies.
Common conditions associated with TRIO (Varvagiannis et al.) include:
TRIO-related neurodevelopmental disorder (TRIO-NDD) due to loss-of-function variants typically characterized by microcephaly;
TRIO-related neurodevelopmental disorder (TRIO-NDD) due to gain-of-function variants typically characterized by macrocephaly or relative macrocephaly.
How could it happen?
The majority of mutations are de novo.
A de novo variant is defined as a small change in the genetic information, which cannot be found in the parents DNA, but in the DNA of the child.
This change is therefore completely novel.
Which are the possible conditions associated with TRIO gene mutations?
Some possible conditions associated with TRIO gene mutations include the following.
global developmental delay
intellectual development disorder
poor speech
infant feeding difficulties
microcephaly or macrocephaly
neurobehaviour problems (ADHD or autism)
dental abnormalities
high palate
scoliosis
skeletal hand abnormalities
seizures
gastrointestinal manifestations
cardiac anomalies
Importantly these do not occur in all people affected by the mutation and there is varying severity.
To outline a profile of diseases potentially associated to TRIO gene mutations, with the support of our community we are collecting information. In the chart below we report the most recurrent clinical characteristics (107 participants).
Please click below to open the most comprehensive guide regarding Clinical Features, Diagnosis/Testing, Management, Genetic Counseling for TRIO-Related Neurodevelopmental Disorders updated March 2023
Team TRIO wants to support research in order to define a more complete clinical picture of individuals affected by the TRIO gene mutation and we invite everyone to contribute.
Find more about this on the Research section of this website by clicking on the following button.
How many cases there are in the World?
TRIO gene mutations are VERY rare!
So far we know approximately 200 people with TRIO mutations worldwide. In the literature at least 157 different variants are reported ( Gene: TRIO - sfari.org ).
Most are children but some are adults too.
We believe that there are many more people with TRIO mutations and that as testing and knowledge improves, more people will be diagnosed.
Do all TRIO gene mutation variants affect health and development?
Only a reduced percentage of variants cause genetic disorders while many others have no impact on health or development.
For example, some variants alter a gene's DNA sequence but do not change the function of the protein made from the gene.
Gene variants can be classified into one of five groups:
Pathogenic: The variant is responsible for causing disease. There is ample scientific research to support an association between the disease and the gene variant. These variants are often referred to as mutations.
Likely pathogenic: The variant is probably responsible for causing disease, but there is not enough scientific research to be certain.
Variant of uncertain significance (VUS): The variant cannot be confirmed to play a role in the development of disease. There may not be enough scientific research to confirm or refute a disease association or the research may be conflicting.
Likely benign: The variant is probably not responsible for causing disease, but there is not enough scientific research to be certain.
Benign: The variant is not responsible for causing disease. There is ample scientific research to disprove an association between the disease and the gene variant.
Evaluation needs to be done for each variant. Just because a gene is associated with a disease, does not mean that all variants in that gene are pathogenic. Additionally, evaluation of a variant needs to be done for all diseases with which it is thought to be associated.
It is important to re-evaluate variants periodically; the classification of a variant can change over time as more information about the effects of variants becomes known through additional scientific research.
The following graphics represent the percentages and the numbers of known TRIO gene variants that may cause pathologies (Pathogenic) or not (Benign) gathered from different sources.
Variants in TRIO with known pathogenicity
Total classified variants (UniProt, ClinVar, LOVD, MitoMap, VarSome & PubMed)
Last update: 22nd February 2024