Autism

Autism, also known as Autistic spectrum disorder (ASD) or Pervasive Development Disorders (PDD) is a syndrome with multiple genetic and non-genetic causes. It is a neurodevelopmental disorder characterized by impairments in three major aspects: 1) social interactions; 2) language and communications and 3) repetitive patterns of interests and activities. These symptoms may range from quite severe (autism) to relatively mild (Asperger syndrome). Epidemiologic studies have implicated some environmental factors such as exposure to toxins, teratogens, perinatal insults and prenatal infections. However, twin and sibling studies have demonstrated strong genetic factors involved in autism. Genome-wide screens in multiplex families have suggested involvement of many genes in the causation of autism. The most common identified regions are present in six different chromosomes, 4, 7, 10, 16, 19 and 22.

Autism can also occur in the presence of various neuropsychiatric, neurologic, and genetically determined conditions. A literature survey of such co-occurrences reveals numerous associations including tuberous sclerosis, fragile X syndrome, Joubert syndrome, Moebius syndrome, fetal valproate syndrome, Down syndrome, Cohen syndrome, Chiari malformation, schizophrenia etc.

The genetic factors associated with ASD include two lines of hypothesis, one involving numerous rare genetic mutations and the other involving fewer, but common genetic variation. Faculty members at the Hussman Institute for Human Genomics (HIHG) (led by Drs. Margaret Pericak-Vance, Michael Cuccaro and John Gilbert) are performing research studies to identify these genetic factors.

In two recently published collaborative studies, the members of HIHG comprehensively tested the common variant hypothesis. A genome-wide association (GWAS) study using a discovery data set of autistic Caucasian families indicated a risk locus at chromosome 5. This novel region on chromosome 5p14.1showed significance in both the discovery and validation data sets, further supporting the hypothesis that complex genetic architecture of autism involves common variation. In a second collaborative GWAS study, two genes encoding neuronal cell-adhesion molecules, revealed strong association signals in cohort of families with affected children and controls of European ancestry. These gene signals were replicated in two independent cohorts. Thus, these findings demonstrate that genome-wide significant association of common variants with susceptibility to ASD.

Currently, we are expanding efforts to include families from diverse racial and ethnic backgrounds. By finding the genes that cause Autistic disorder, we hope to gain valuable insights into how autistic disorder develops. In addition, finding the genetic causes of autistic disorder will hopefully lead to better diagnostic and treatment modalities.

Contact Information
View our Autism brochure