What does “spectrum” mean in Autism Spectrum Disorder? In this video, we explore how the term reflects both behavioral differences and complex genetic causes. India’s largest autism genetics study found that nearly 1 in 3 children have a clear genetic reason — often due to a de novo mutation, a new genetic change not inherited from parents. The interview explains how such findings help families plan better, access potential treatments, and prepare for future pregnancies. Science is now helping decode autism — not just to understand it, but to manage it with hope.

Shahid Akhter, Editor, HealthYouOnline, spoke to Dr. Harsh Sheth, Head of the Advanced Genomic Technologies Division at the Frige Institute of Human Genetics, Ahmedabad, to understand the genetic basis of Autism Spectrum Disorder (ASD), including the role of de novo mutations, Fragile X, MECP2, and how these insights are helping families with diagnosis, treatment, and reproductive planning. Harsh Sheth

Autism Spectrum Disorder: Why Spectrum ?

The word spectrum is present because of two reasons. Number one, these children do not necessarily look exactly the same. Some may have stereotypes. It means they would either shake the hands like this or rub the hands like this. Some may be able to talk; some may not be able to speak even simple words by the time they are a couple of years old.

Because of that, it's called a spectrum. The other reason why it is called a spectrum is because of the underlying genetics. These diseases are not caused by just one gene. They are caused by thousands of genes. And if any one of them goes haywire, you end up with a disease, what we call autism spectrum disorder today.

Autism: Genetic base

So since 1990, a lot of people have tried to understand whether autism really has a genetic basis or not. And in fact, there is a genetic basis to autism for sure. In one of the largest studies and the very first one that was done in India, and it was co-led by myself, we ended up showing that in nearly one out of every three cases that walk into the clinic presenting with autism, there is a genetic cause.

There were thousands of genes that are involved in the development of the brain. Now, what we have identified is that there are a couple of genes that are, what do you call them, the usual suspects? The most common one is the fragile X retraction gene, which is generally mutated in the males. Only the second one, which is very common, is MCP two. Now it's generally girls who are presented with mutations in this gene and not boys. It's lethal for boys. Beyond that, there are hundreds to thousands of genes. Any one of which is mutated would lead to autism spectrum disorder.

Autism: De novo mutations -

So the largest study that was done to date showed that in children where a genetic diagnosis was made in 70% of the cases, it was because the mutation was only present in the child. That mutation was not inherited from either of the parents. What that simply means is it's also, by the way, called a de novo mutation in medical literature. 

It means that when either the sperm or the egg was being formed, the DNA that was in there somehow got mutated, and that mutation is now only present in the child. The parents don't have it. So if, for example, the parent is planning for another pregnancy down the line and the first child had a de novo mutation, the risk of the second child having a similar mutation remains less than 2%.

De novo mutation: What the future holds

What it means for the child is that now that they have a clear-cut genetic diagnosis, there are 2 or 3 critical benefits that come to them. For example, if a child is diagnosed with a dino mutation in the MCP2 gene, which is involved in Rett syndrome, there is a treatment available for them called dystrophin a tight right.

So it helps in identifying whether the child could get a reasonable treatment that is available as of now. The second one is for the parents: when the plan for the second pregnancy, would the child have a similar disease or a similar gene getting mutated or not? And the third one is that when this child grows up and plans his or her family's future ahead, the same genetic test result would help them plan for the reproductive life ahead.  

De novo mutation: future inheritance

So if a child has a de novo mutation, and when it's their chance to have a reproductive life, then the risk of their child inheriting this mutation increases to 50%. In the remaining 50% of the cases, the child would be completely normal. If it's a scenario whereby a child has inherited both faulty copies of the DNA from both of the parents and his or her partner are completely healthy, then the risk of their child having autism drops down to 2%. 

Autism: Impact & Management

So we went from understanding why autism occurs. What is the genetic basis for it? Now is the time to think about treatments. And this is where the world is moving into to try and understand how these mutations impact the structure of the brain and how we can design treatments to ensure that despite these issues in the brain structure development or synaptic development, we can remodel them in a way that this child can have a happy, healthy future?