Researchers at the University of Alabama at Birmingham have found a new genetic mutation as the likely cause of a condition that left a woman in her 20s unable to walk.
UAB’s Undiagnosed Diseases Program made the discovery, which is reported in the Sept. 9 issue of Neurology, the journal of the American Academy of Neurology. UAB announced the findings in a press release.
The woman began having problems at age 5 and by adulthood could not walk, had hand tremor, leg spasms, intermittent slurred speech and occasional tingling in her fingers and toes. She was evaluated in the Department of Genetics at UAB’s Undiagnosed Diseases Program.
Researchers conducted an exhaustive review of symptoms and family history and tests to rule out possibilities.
The patient underwent whole genome sequencing and variant analysis at HudsonAlpha Institute for Biotechnology. That revealed a previously unknown mutation in the ADCY5 gene.
Other variants of the same gene have been linked to childhood movement disorders. The woman’s parents did not have the mutation, indicating it was a spontaneous mutation in the woman.
Dr. Marissa Dean, assistant professor in the Department of Neurology and the first author of the case study, said the woman’s diagnosis was dystonia with spastic paraparesis, likely caused by the variant in the ADCY5 gene, a finding that follows the guidelines of American College of Medical Genetics and Genomics.
Dean said there is no treatment to reverse the condition but having a diagnosis often gives patients and families closure and relief. Dean is overseeing supportive therapy for the patient, including physical and occupational therapy and medications for muscle spasms and stiffness.
Dr. Bruce Korf, UAB’s chief genomics officer and director of the Undiagnosed Diseases Program, said finding the cause of a rare condition can lead to more breakthroughs.
“The discovery of a new variant of a gene is extremely important,” Korf said. “Every piece of information that we can decipher sheds a bit more light on our understanding of genetic disease.”
Co-authors on the case study from UAB are Korf, Ludwine Messiaen, Ph.D., Dept. of Genetics; Salman Rashid, M.D., Dept. of Pediatrics; and David Standaert, M.D., Ph.D., Dept. of Neurology. Co-authors from HudsonAlpha Institute for Biotechnology are Gregory M. Cooper, Ph.D., and Michelle D. Amaral, Ph.D.