New insights into genetic disorders: the discovery of Seaby-Ennis Syndrome

Dr. Eleanor Seaby, a paediatric doctor and former University of Southampton PhD student, has made a significant breakthrough in the field of genetics, recently published in Brain. Her research focuses on the DDX17 gene, which – when mutated – is linked to a newly-identified condition known as Seaby-Ennis Syndrome.

Discovery of Seaby-Ennis Syndrome

Using data from the 100,000 Genomics Project , Eleanor identified that patients with mutations in the DDX17 gene exhibit a neurodevelopmental disorder, now officially named ‘Seaby-Ennis Syndrome.’ This condition affects gross motor and fine motor skills, speech and language development, behaviour and can be accompanied by facial abnormalities.

“I chose the name Seaby-Ennis Syndrome to honour the contributions made by myself and my supervisor, Professor Sarah Ennis, in the discovery of this condition. This recognition is particularly important for enhancing the representation of disabled women, like myself, in the field of science,” explained Eleanor.

Collaborative research journey

During her PhD, which was jointly supervised by the University of Southampton and the Broad Institute of MIT and Harvard University , Eleanor focused on identifying new disease genes. Through her research, she identified 18 new potential disease genes, 13 of which are now proven.

“The challenge with identifying new genetic conditions,” Eleanor explained, “is that it takes a long time to prove each one, requiring significant funding and resources. This creates a bottleneck in diagnosing children with genetic disorders.”

Currently, there are approximately 5,000 known genetic diseases. Eleanor noted, “many patients and families lack a genetic diagnosis because we are yet to understand the clinical and biological consequences of mutations in all human genes. I felt it was critical to drive this research forward during my PhD to help patients and families who have been left without a diagnosis or any treatment options.”

After identifying the DDX17 gene, Eleanor built an international cohort of 11 patients exhibiting similar genetic alterations and developmental delays. Eleanor and her supervisor, Professor Sarah Ennis , also engaged international scientific collaborators, including Professor Matt Guille from the University of Portsmouth , and Drs. Cyril Bourgeois and Dr. Julien Courchet from the University of Lyon .

Sarah commented, “this project relied heavily on collaboration. Our partners helped model these genetic changes in animal models. We observed neurodevelopmental and behavioural alterations in both mouse and frog models, supporting our findings in humans.”

Looking to the future

The identification of Seaby-Ennis Syndrome marks a critical advancement in the understanding of neurodevelopmental conditions. “This discovery is hugely important,” Eleanor noted. “By identifying this genetic disorder, we can provide more diagnoses and bring hope to affected families.”

She added: “The first step in understanding genetic disorders is pinpointing the gene that drives the disease. With further research, we can learn how that gene impacts the condition.”

Read the full article, Monoallelic de novo variants in DDX17 cause a neurodevelopmental disorder , published in Brain , here .