Teams of Researchers Discover Gene for Spasmodic Dysphonia
Christine Klein, MD, Professor of Neurology and the Schilling Professor of Clinical and Molecular Neurogenetics at the University of Lubeck, Germany, was the principal investigator of an international study group that has identified the DYT4 gene associated with a dominantly inherited form of dystonia called whispering dysphonia. Dr. Klein is a past member of the DMRF’s Medical & Scientific Advisory Council and guest author for the Dystonia Dialogue. Whispering dysphonia caused by the DYT4 gene is an inherited form of dystonia, causing muscles to contract uncontrollably first in the vocal cords and then progressing to the neck muscles.
Expanding on previous work on DYT4, Dr. Klein and her team conducted genome-wide linkage analysis in 14 members of a large Australian family followed by genome sequencing in two individuals. The findings were published online in December in the Annals of Neurology along with a second article describing another research team’s work on this gene, led by Henry Houlden MD, MRCP, PhD, Professor of Neurology and Neurogenetics, The National Hospital for Neurology and Neurosurgery Institute of Neurology Queen Square, London.
Symptoms of spasmodic dysphonia (sometimes referred to as laryngeal dystonia) include involuntary contractions of the vocal cords muscles, causing interruptions in speech and affecting voice quality. One of the most characteristic features of spasmodic dysphonia is the patterned, repeated “breaks” in speech, causing a strangled-sounding or breathy voice. Treatment may include botulinum neurotoxin injections, voice therapy, and breathing techniques.
The DMRF congratulates Dr. Klein, Professor Houlden, and the outstanding investigators who contributed to this exciting discovery. Each new gene associated with dystonia provides a potential new target for therapeutics and adds to science’s growing understanding of all the dystonias.
Mutations in the autoregulatory domain of β-tubulin 4a cause hereditary dystonia
Joshua Hersheson, Niccolo E. Mencacci, Mary Davis, Heather N MacDoanld, Daniah Trabzuni, Mina Ryten, Alan Pittman, Reema Paudel, Eleanna Kara, Katherine Fawcett, Vincent Plagnol, Kailash Bhatia, Alan J Medlar, Horia C Stanescu, John Hardy, Robert Kleta, Nicholas W. Wood and Henry Houlden
Accepted manuscript online: 13 DEC 2012 04:43AM EST | DOI: 10.1002/ana.23832
Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene
Katja Lohmann, Robert A Wilcox, Susen Winkler, Alfredo Ramirez, Aleksandar Rakovic, Jin-Sung Park, Björn Arns, Thora Lohnau, Justus Groen, Meike Kasten, Norbert Brüggemann, Johann Hagenah, Alexander Schmidt, Frank J Kaiser, Kishore R. Kumar, Katja Zschiedrich, Daniel Alvarez-Fischer, Eckart Altenmüller, Andreas Ferbert, Anthony E Lang, Alexander Münchau, Vladimir Kostic, Kristina Simonyan, Marc Agzarian, Laurie J Ozelius, Antonius PM Langeveld, Carolyn M Sue, Marina AJ Tijssen and Christine Klein
Accepted manuscript online: 13 DEC 2012 04:42AM EST | DOI: 10.1002/ana.23829