News Release

Cholesterol accumulation contributes to genetic movement disorder

Family finds hope in research breakthrough for rare diagnosis

Peer-Reviewed Publication

Greenwood Genetic Center

Cholesterol accumulation in zebrafish with NUS1 variants

image: Confocal images of the zebrafish hindbrain and tail comparing cholesterol accumulation in wild type zebrafish (top), and zebrafish with the NUS1 mutation before (center) and after treatment (bottom). Zebrafish displayed reduced cholesterol accumulation after treatment. view more 

Credit: Greenwood Genetic Center

Greenwood, SC (March 22, 2021) - A research team at the Greenwood Genetic Center (GGC) has identified the mechanism that causes movement disorders in patients with mutations in the NUS1 gene. Using both cellular and model organism studies, cholesterol accumulation was found to contribute to the symptoms of seizures, ataxia, and movement abnormalities. This breakthrough study on NUS1, a gene that has also been potentially linked to Parkinson's Disease, is reported in the current issue of Genetics in Medicine, the Journal of the American College of Medical Genetics and Genomics.

Chloe Murphy, 15, of Bluffton, SC began experiencing tremors at age three. Through the years she has also experienced seizures, atypical eye movements, learning delays, and balance issues. Initial genetic tests were normal until, at 12 years of age, whole exome sequencing identified a de novo variant in NUS1.

"Chloe's specific NUS1 variant had never been reported before, so we initiated functional studies using fibroblasts, and developed a zebrafish model to mimic her genetic variant," said Heather Flanagan-Steet, PhD, Director of Functional Studies and Director of the Hazel and Bill Allin Aquaculture Facility at GGC. Flanagan-Steet and her team also studied two other patients with NUS1 variants and similar clinical findings.

Chloe's zebrafish 'avatar' displayed aberrant motility and swimming patterns. Cellular studies also identified increased lysosomal cholesterol storage, both in the skin cells of the three patients as well as in the cells of the zebrafish avatar.

"These studies confirmed the pathogenicity of this variant, which provided a long-awaited answer for her family, and also gave us the opportunity to better understand this rare diagnosis and consider potential treatments," said Rich Steet, PhD, Director of Research at GGC.

"The excess cholesterol storage in both the human and zebrafish cells, suggested that treatments targeting cholesterol accumulation could be therapeutic," said Flanagan-Steet. "When we treated the affected zebrafish with the drug, 2-hydroxypropyl-beta-cyclodextrin, they showed reduced accumulation of cholesterol and significant improvement in swimming behaviors, suggesting that the cholesterol accumulation is at least partially responsible for the motility phenotypes."

The Murphy family has found hope through their research participation.

"Our journey so far has been to find the 'why.' We felt like once we could determine this, we could better understand what could help Chloe," said her mother, Jessica. "Our hope now is that these breakthroughs with NUS1 will lead to a solution to improve her health."


This work was supported by the Greenwood Genetic Center and a grant from the National Institutes of Health.

About Greenwood Genetic Center

The Greenwood Genetic Center (GGC), founded in 1974, is a nonprofit organization advancing the field of medical genetics and caring for families impacted by genetic disease and birth defects. At its home campus in Greenwood, South Carolina, a talented team of physicians and scientists provides clinical genetic services, diagnostic laboratory testing, educational programs and resources, and research in the field of medical genetics. GGC's faculty and staff are committed to the goal of developing preventive and curative therapies for the individuals and families they serve. GGC extends its reach as a resource to all residents of South Carolina with satellite offices in Charleston, Columbia, Florence and Greenville. For more information about GGC please visit

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.