Understanding Genetics: X-Chromosome

As you may know the X chromosome plays a role in the sex of an individual. The X chromosome is contributed by the mother or father, depending on the sex of the child. A girl will have XX genetics and a boy will have XY genetics. My family has a history of Autism that is newly discovered. My son, Aiden, is the first documented case and shortly after his diagnosis my little brother, Will, was diagnosed with Autism. Both are high functioning. I do not have Autism, my daughter, Haley, is showing no signs of Autism and there is no history of Autism in my husband's family. I think Autism is linked to the female side of my family, me, my mother, my maternal grandmother, etc all carry the Autism gene. So what are the real numbers? How likely is it that the X chromosome contributes to Autism?

This color coded picture flow chart will help you understand how the X chromosome behaves across multiple generations. 

Shared X

Let’s explore Autism from the X chromosome. About published an article in 2007 citing a study from Newsday; the researchers discovered that mother's who carry the Autism gene do not exhibit the traits of Autism themselves but have an approximate 50% chance of passing the trait to their children. The IAN network also has published a study referencing this information. New theories suggest that Autism is a "spontaneous mutation" of genetics, but IAN cites the strong family history in some individual families. They further suggest that men can be carriers of Autism, but if men carry the genes they are more likely to exhibit the signs of Autism than women. IAN states if either parent carries the autism-causing mutation than their children will have a 50/50 chance of inheriting that mutation. A girl, who does not show signs of Autism, may still carry the mutation and has a 50% chance of passing it onto her children. Her daughter will be far less likely to show signs of Autism and so on. 

This SFARI article references a 2011 study originally published in Molecular Autism. The researchers have located a gene on the X chromosome named TBL1X. Researchers functioned under the theory that Autism is related to the X chromosome because the disorder is approximately four times more common in boys than girls. Since boys only inherit one X chromosome several independent studies have investigated mutations on the X chromosome in relation to Autism. This study included approximately 5,856 individuals from 1,456 families with one or more children with Autism. They found a variant linked to the TBL1X gene, but only in males with Autism. 

Also in 2011, at the 12th International Congress of Human Genetics, research was presented that shows deletion of a part of TMLHE gene on the X chromosome found in a significant statistical number of males with Autism. This is something to be excited about since researchers believe that Autism associated with a lack of TMLHE can be prevented or partially reversible with proper dietary supplementation. It is important to understand that TMLHE deficiency is not a common cause of Autism, researchers determined. TMLHE deletion can be found in typically developing males at a rate of 1 in every 350, but the frequency of this deletion was approximately 3 times higher in Autistic males. In mothers also diagnosed with Autism this deletion was found in 6 out of 7 autistic siblings had this deletion. This is a very important and significant finding. Researchers conclude that as many as 1 in approximately 150 individuals with Autism have the TMLHE deletion. 

What about twin studies? In 2012 the University of Florida released information on Genetics and Autism; they estimate that in 80-85% of Autistic cases have an unknown or multifactorial cause. They also estimate that 3% are cause by a single inherited gene and approximately 5% are due to chromosome anomalies. They do address the genetic link to Autism and cite proof through twin studies. In identical twins the likelihood of both having Autism is as high as 90%. They further investigate the high recurrence of Autism in relatives close to the Autistic individuals. For instance parents or siblings with Autism will determine a risk of approximately 3-6% to a sibling or child. U of F also agrees that the excess of male prevalence in Autism suggests an X-chromosome contribution. 

There are three medical conditions with strong ties to Autism which also have strong impacts to the X-chromosome: Turner syndrome, Klinefelter syndrome, and Fragile X syndrome. 

Turner Syndrome: This disorder is a chromosomal condition that affects females. Turner syndrome is related to the X-chromosome and is the result of one X missing. So a female child with Turner's will have a X genetic footprint instead of an XX genetics. In some cases the missing X will be partially missing or simply rearranged. Most cases of Turner's are not inherited. Turner syndrome shares a common phenotype with Autism. Individuals with Turner's have difficulty recognizing fear on the faces of others. Autistic individuals appear to have difficulty in identifying facial expressions. Doctors at the National Alliance for Autism Research (NAAR) are currently conducting further research into this based on the information found by the Brain Science Unit at the Institute of Children Health in London. Doctors there have discovered a region on the X-chromosome that is related to facial recognition phenotype. By investigating this one trait of Turner's researchers hopes to identify why and relate that to Autism. Turner syndrome occurs in approximately 1 in 2,500 female births. 

Turner Syndrome

Klienfelter Syndrome: This is also a chromosomal condition that affects males. People typically have two sex chromosomes, either XX (girls) or XY (boys), those with Klienfelter have XXY sex chromosomes (there is a variant: XYY). There is an extra X copy present which interfere with testosterone production along with intellectual disability and other physiological impacts. Behavior problems in those suffering from Klienfelter have been associated with Autism. According to Opening Autism approximately one in 10 diagnosed with Klienfelter's is also diagnosed with Autism. This is also a random occurrence with no chromosomal changes. Klienfelter's affects approximately 1 in 660 men. 

Klinefelter Syndrome

Fragile X Syndrome: This genetic condition can cause a range of problems from behavioral to cognitive impairment. Males are most severely affected by this disorder, but it can also impact females. Fragile X is inherited through mutated genes on the X chromosome. Approximately 1 in 4,000 males and 1 in 8,000 females are affected by Fragile X Syndrome. Approximately 15-33% of those with Fragile X also have Autism, according to the National Fragile X Foundation, making up approximately 2-6% of the Autism community. When an individual with Fragile X is also diagnosed with Autism, the Autism is also caused by the mutation in the Fragile X gene. Here is an interesting video on Fragile X.

Fragile X Syndrome

It is important to understand that everyone with Autism does not have a serious medical condition such as Turner's, Klinefelter's or Fragile X, and not everyone with these conditions has Autism. It is interesting to correlate the impact Autism has on the X chromosome, which also influences these disorders. To read more about the X chromosome and Autism I suggest you read this article from Social Cognitive and Affective Neuroscience. 

I hope this helps you understand the impact of the X chromosome in Autism and its potential contribution to your case. With understanding and education we can push forward. 

We, at Aiden's Heroes, are always here to support you on your Autism journey.