Elliott Sherr (MD, Professor in Neurology and Pediatrics, Institute of Human Genetics and the Weill Institute of Neurosciences, University of California, San Francisco, UCSF)
Prof Elliott Sherr is a Child Neurologist and co-directs the Comprehensive Center for Brain Development at UCSF. His research team studies the genetic and biological mechanisms of disorders of brain development including epilepsy, autism and agenesis of the corpus callosum. They have found that both inherited and non-inherited (i.e., spontaneous) genetic events play an important role in causing brain malformations.
Prof Sherr described how the field of genetic testing has moved rapidly in the last 15 years. In 2003, the state of the art in genetic testing involved looking at chromosomes under a microscope; however our knowledge of genetic disorders was limited – testing 100 individuals would only result in about 8 receiving a genetic diagnosis. Modern sequencing tools have transformed the way that geneticists have been able to identify specific gene mutations, with around 30 to 45% of individuals with ACC now having an identifiable genetic cause. The likelihood of receiving a diagnosis increases if the individual has several congenital abnormalities, such as heart or vision defects. ACC is well known to have a wide range of outcomes and this variability is likely to be related to the diversity in genetic causes that have been found.
Knowing more about which specific genes influence the development of the corpus callosum allows for a better understanding of ACC and can remove a large amount of uncertainty for families. Receiving a genetic diagnosis can also impact on other areas of family life including future treatment options, social support and family planning. As a case example, Prof Sherr described the recent discovery of the DDX3X gene mutation, which primarily affects girls due to its location on the X-chromosome. It has been identified in about 200 individuals to date and may be the cause of 1 to 3% of all intellectual disabilities in females. The DDX3X gene mutation has also been linked to seizures, autism, low muscle tone, abnormalities of the brain such as a thinner corpus callosum, and slower physical developments. The discovery of this gene mutation has led to the establishment of the DDX3X Foundation, a non-profit organisation, which is dedicated to supporting research, connecting families, and raising awareness.