HudsonAlpha researchers identify genetic variants that cause intellectual delay

Matchmaking website helped connect international research team for project

Huntsville, Ala. — Researchers at the HudsonAlpha Institute for Biotechnology, along with an international team of collaborators from six countries, have identified a new genetic disorder that causes intellectual and developmental delay in children. GeneMatcher, an online “matchmaking” system for scientists researching rare genetic variants, connected the team members. The research is published online December 22 in the American Journal of Human Genetics (AJHG).

“Essentially, we did experiments to understand how variants in the EBF3 gene might change its function during development,” said Drew Hardigan, a graduate student in the Myers Lab at HudsonAlpha and a co-lead author. “The role of EBF3 had been studied in terms of neural development, but had not been previously described as a gene in which mutations cause intellectual and developmental delay. We were able to demonstrate that changes to the gene are the cause of a clinical disorder.”

EBF3 was identified at HudsonAlpha as an interesting gene for research through a pediatric genomics program led by Greg Cooper, PhD, a faculty investigator at HudsonAlpha and a senior author for the AJHG publication. Through genomic sequencing and analysis, Cooper’s lab had identified two patients with changes to EBF3. However, his team could not find any similar cases or publications on the gene to confirm the variants were causing the patients’ symptoms. The genetic changes were labeled variants of uncertain significance, or VUSs.

The group turned to the website GeneMatcher, which operates like a matchmaker site for scientists interested in genetic variants. Using the online system, Cooper’s team was able to contact researchers around the world who were also interested in VUSs in EBF3. Once connected, the international group performed a statistical analysis confirming the gene was very likely the cause of the symptoms for 10 patients located on three continents. The group then used a variety of genomic assays to investigate the function of the variants.

“Our experiments help support the statistical data biologically,” Hardigan said, “providing clues to further understand the role of this transcription factor for normal neuronal function.”

As the group explain in their paper, the experiments demonstrated that the genetic changes to EBF3 – the same changes found in those 10 patients – disrupt important functions required for normal development. They also found that changes in this gene were likely the cause of about one in every 1,000 patients with unexplained neurodevelopmental disorders.

“We were able to combine statistical and computational analyses of genetic data with the results of biological experiments to provide these 10 patients with an answer,” said Cooper, the HudsonAlpha investigator whose pediatric genomics research began this scientific journey. “While this particular diagnosis may not have a simple treatment, these families can stop the often long and costly process of medical testing and specialist visits that accompanies having an undiagnosed disease. It’s an honor to be able to help in even a small way with these significant medical challenges.”

About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to innovating in the field of genomic technology and sciences across a spectrum of biological challenges. Opened in 2008, its mission is four-fold: sparking scientific discoveries that can impact human health and well-being; bringing genomic medicine into clinical care; fostering life sciences entrepreneurship and business growth; and encouraging the creation of a genomics-literate workforce and society. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. Designed to be a hothouse of biotech economic development, HudsonAlpha’s state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. The relationships formed on the HudsonAlpha campus encourage collaborations that produce advances in medicine and agriculture. Under the leadership of Dr. Richard M. Myers, a key collaborator on the Human Genome Project, HudsonAlpha has become a national and international leader in genetics and genomics research and biotech education, and includes more than 30 diverse biotech companies on campus. To learn more about HudsonAlpha, visit:

HudsonAlpha Media Contact:
Margetta Thomas