Autism-related syndrome discovered

23 February 2013

CNCR and NCA researchers discover a new autism-related syndrome by combining clinical and fundamental research.

A multidisciplinary team of scientists at Clinical Genetics and Functional Genomics have discovered that genetic defects in the AUTS2 gene cause mental retardation. In addition to intellectual disability, affected people often have a typical appearance including a small head size and short stature.

In total, the genetic composition of 50,000 subjects with autism or intellectual disability was studied in medical centers and laboratories from the Netherlands, Belgium, the United Kingdom, Canada and America. Of these, 24 subjects carried a similar defect that disrupted the function of the AUTS2 gene. After detailed investigation, the clinicians recognized common features shared by multiple patients with the genetic defect. This list of features can be used to recognize new patients with the so-called AUTS2-syndrome.

Remarkably, a specific part of the AUTS2 gene appeared to be extra important: defects occuring in that part caused more severe variants of the syndrome.

To study the gene function in more detail, an American research group generated zebrafish with a similar gene defect. These fish showed the same abnormalities as the human patients, including the small head size. The results point out that the gene is required to generate new nerve cells during brain development. The fish could be ‘cured’ by providing the human AUTS2 gene to the fish, even when only the extra important part of the human gene was given.

On average, one out of fifty subjects in the Netherlands suffers from intellectual disability. In many cases this condition originates from changes in the genetic material, but in most cases it is unknown which genes are involved. For this rare syndrome, the gene has now been identified.

This publication is the result of cooperation between the Department of Clinical Genetics (VU Medical Centre) and the Department of Functional Genomics (Faculty of Earth and Life Sciences).