New discoveries of genetic mutations link autism, schizophrenia, certain seizure disorders, and certain intellectual disabilities as stemming from a common origin. Currently, each of these disorders is treated in ways entirely different from the others but further research could change that. It might be possible someday to diagnose these illnesses from a molecular perspective rather than from observational evaluation. Molecular diagnosis, in turn, could lead to improved treatment methods that target the molecular starting point of the disorder rather than merely attempt to ease symptoms.

Dr. Shane McCarthy and Professor Aiden Corvin are collaborators in the genetic study that links two nations: the United States and Ireland. McCarthy is affiliated with Cold Spring Harbor Laboratories (CSHL) in New York and Corvin is with Trinity College in Dublin. Their research involves trio families, epigenetics, the exome, and de novo mutations (DNMs) that affect just five individual genes.

Trio Families

The research team enlisted 57 trio families for the study. A trio family includes a child and his or her biological parents.


Epigenetics is the study of gene expression, or what causes a gene to turn on or off to produce a specific effect. An example of natural epigenetics is when a child is tall like one parent rather than short like the other.

External factors influence gene expression by altering or enhancing the epigenetic factors of the child’s DNA. Exposure to cigarette smoke while in the womb, for example, could alter the child’s natural epigenetic expression of genes that promote healthy lung development. The child may develop respiratory issues and, if a smoker, be at greater risk for lung cancer.

The Exome

The word genome is a combination of the words gene and chromosome. The genome represents all the genetic material — all the DNA — in an organism such as a human.

The exome is a very tiny portion of the genome, no more than about 4% of all the genetic material in an organism. The exome represents only the genetic material that regulates the creation of proteins.

De Novo Mutations

“De novo” is the Latin term for “from new,” indicating the mutations are new. In a trio family, the child is said to have de novo mutations if his genome contains genetic mutations found in neither of his parents’ genomes. The mutation is new to the child, not inherited.

Mutations in the McCarthy / Corvin study trio families were:

  • 42 DNMs for schizophrenia and/or psychosis in the child but not in either parent
  • 15 inherited mutations for psychosis that runs in the family

Five Genes

The DNMs in the 42 children occurred in three genes previously linked to autism:

  • AUTS2
  • CDH8
  • MECP2

and two genes linked to intellectual disabilities:

  • HUWE1

These five genes are called overlapping genes, as their performance affects various disorders. Three of them are epigenetic marks, controlling when specific genes are turned on or off.

According to McCarthy, identifying specific exome sequences linked to disease provides fresh biological insights that might make it possible to develop targeted therapeutic options for an entire range of psychiatric disorders.

Source: McCarthy, SE, et al. “De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability.” Molecular Psychiatry. Macmillan Publishers Limited. Jun 2014. Web. Jun 3, 2014.