GENE MUTATIONS AND SYMPTOMS IN AUTISM SPECTRUM DISORDER

Diversity in genotype underlies diversity on the surface

Lirio S. Covey, PhD.

Source: Jonathan Chang, Sarah R Gilman, Andrew H Chiang, Stephan J Sanders, Dennis Vitkup. “Genotype to phenotype relationships in autism spectrum disorders”. NatureNeuroscience, published online 22 December 2014.

Has it struck you that persons with autism whom you have met are so different from one another? Indeed, many of us in the autism community are very familiar with the theme of – different, not less.

True, there are commonalities – a tendency towards compulsive and repetitive behaviors, problematic adjustment to change, inability to sense other people’s feelings, awkwardness in social settings.

But there is also a broad range of differences – in language capacity, emotional stability, mental strength, functioning skills, including physical appearance. (Unlike persons with Down’s syndrome or Rett’s disorder who show physical features characteristic of their respective condition).

A recent study conducted by researchers at Columbia University in New York indicates that such differences, apparent on the surface and referred to as phenotypical differences, relate to broad heterogeneity on the genetic level. These differences can be traced to diverse mutations occurring to any or combinations of hundreds of genes found to increase the risk of autism. Gene mutations are alterations in the DNA sequence, usually rare and different from what occurs in most people. Different mutations can lead to different features of ASD.

The diversity in genetic mutations is thought to underlie the broad range in severity of ASD impairments and in the large male to female ratio of ASD (4:1). More active mutations relate to greater severity of ASD symptoms. Thus, milder mutations characterize high functioning ASD persons, whereas greater mutation activity characterizes greater impairment such as low-verbal or nonverbal IQ.

The threshold for damaging gene mutations also appears to be higher in girls than boys, consistent with the lower prevalence of ASD in girls than boys. However, when mutated genes occur in girls they have greater activity than in boys, consistent with the observation that ASD symptoms, when they occur, are more severe in females than in males with autism.

These findings have implications for ASD management and treatment. According to the senior author, Dr. Vitkup, “through understanding of the relationships between genetic mutations and phenotypical features of ASD we may be able to use patients’ genetic profiles to develop diagnostic and prognostic tools and perhaps personalize treatment”.