top of page
Search

Genetic Mutations Behind Autism: Why Gender Matters

As I was researching my previous blog on the neurological impacts of Autism Spectrum Disorder, I came across many sources discussing the genetic determinants of Autism. I found research shows a strong correlation between specific genetic mutations and Autism. Today’s blog will explore some of those specific mutations and how those mutations can differ between genders.


According to UCLA Medical School, scientists estimate that anywhere from 200-1,000 different genes are potentially responsible for Autism. By examining karyotypes and using the candidate method, scientists have been successful in finding RELN, Arx, MeCP2, TSC2, UBE3A, NLGN3, and NLGN4, which we will discuss later in this blog, as Autism-causing genes when mutated. In addition, scientists examined synapse-related genes, which, if mutated, can slow down or negatively impact synapses between neurons. The mutations in these genes are often the reasons for the difficulties in social interaction and communication in individuals with Autism, as many of them, such as a mutation in the SHANK3 gene, disrupt prefrontal cortex functioning and connectivity. Since the prefrontal cortex of the brain is responsible for communication and decision-making, these areas may be impaired in people with Autism due to mutations like the one in SHANK3. In addition, for example, mutations in the NLGN3 gene, specifically NLGN3 R451C KI and NLGN3 KO, often result in communication struggles and repetitive behaviors such as twitching we see in individuals with ASD. 


Some genes affect chromosomes, such as the NLGN4 gene, which only affects the X chromosome, so you might think it impacts women more than men. Interestingly that’s not the case and we’ll get into why in the next paragraph, but for now: think about famous people and people in your life with Autism. They’re probably mostly men, right? Do a quick Google search of famous people with Autism, and most of the names are male – Elon Musk, Albert Einstein, Isaac Newton, Bill Gates. Just a few (like Susan Boyle) are women. This review empirically backs up this trend combining data from 54 studies, including 13,784,284 participants, of whom 53,712 had ASD. Of these 53,712 with ASD, 42,792 were boys, and only 9,740 were girls. I was curious if there was a genetic component for this 3:1 ratio.


The fascinating reason for this ratio is a genetic mutation in the NLGN4 gene on the X chromosome, which disproportionately affects males because they only have one X chromosome. Since females have two X chromosomes, one chromosome can often compensate for a mutation of NLGN4 in the other. However, males only have one X chromosome, and there isn’t a gene on the Y chromosome to compensate for an NLGN4 mutation on the X chromosome. This is why we see about three times the number of men diagnosed with Autism compared to women. 


I hope this blog series is giving you a fuller picture behind the genetic causes of Autism Spectrum Disorder and how differences in genetics result in the behaviors we often see in individuals with Autism.  In future blogs I’d like to examine how socioeconomic and other external factors affect rates of Autism diagnoses and outcomes for individuals with Autism.


Sources: 








 
 
 

Comments

bottom of page