Identifying Genes

The Bachmann-Strauss Foundation has funded numerous studies identifying genes associated with dystonia-Parkinsonism syndrome, as well as follow up research to understand the molecular pathways that underlie the diseases. Major genetic discoveries supported by the Foundation include:

- In 1997, a research team led by Xandra O. Breakefield, PhD and Laurie Ozelius, PhD, identified and cloned the DYT1 gene responsible for early-onset dystonia. The discovery reported in Nature Genetics, set the stage for major advances in our understanding of the causes, development and treatment of a severely debilitating form of dystonia that begins in childhood.

- Researchers from London’s University College, Institute of Neurology, led by Professors Nick Wood and Kailash Bhatia, identified mutations in a gene called ANO3 as the possible cause of the most common form of dystonia affecting the neck and face (cranio-cervical dystonia). The researchers found six changes throughout the new gene, ANO3, which might be linked to dystonia. This is the first work implicating an ion channel as the cause of dystonia, and it raises the question of whether medications could be targeted at the channel to compensate for improper functioning, as well as to shed light on the cellular pathways involved in the disease as a whole.

- Discovery of a novel gene, GNAL, for primary torsion dystonia, also known as dystonia musculorum deformans, was made through the collaboration of the molecular genetic laboratory of Dr. Laurie Ozelius, Icahn School of Medicine at Mount Sinai, and a clinical research team led by Dr. Susan Bressman, MD, Director, Bachmann-Strauss Dystonia Center of Excellence and Chair, Department of Neurology, Beth Israel Medical Center, New York. These findings describe the GNAL gene as pointing to pathways in the brain’s dopamine system as the origin of pathophysiology. The research unveils a new potential therapeutic target and an opportunity for developing new treatments, as well as helping in the development of genetic tests to confirm diagnoses, identify unaffected adult carriers, and provide greater reproductive health options for affected families.

- Breaking new genetic barriers, Christine Klein, MD, University of Lubeck, Germany, is characterizing the gene TUBB4 that causes Whispering Dysphonia. This is a rare inherited disorder where an individual is able to talk normally when they’re asleep, drunk or emotional, but for the most part they are only able to whisper. The condition may be progressive and leaves the person unable to make a single sound.

- In 2014, researchers at Mount Sinai Beth Israel, including lead author Rachel Saunders-Pullman, MD, MPH, reported results of genetic screening of dystonia in the Amish-Mennonite population in the journal Movement Disorders. This population is of special interest since the THAP1 gene (also known as DYT6) was originally identified in four Amish-Mennonite families sharing the same “founder” mutation through a common ancestor. The study demonstrated that in addition to this THAP1 founder mutation, different mutations in THAP1 also cause primary dystonia in Amish-Mennonites. Also identified were mutations in the recently described GNAL gene (also known as DYT25), and in the DYT1 (TOR1A) gene. These findings emphasize the range of genetic causes of primary dystonia even within a certain ethnic group.