DMRF-Funded Researchers Discover Unique Dystonia Mutation
Several years ago, DMRF-funded investigator Zbigniew Wszolek, MD of Mayo Clinic Florida began studying a large family with three generations living with adult onset focal dystonia. None of the family members had any of the known dystonia-causing mutations, and this was the first study of late-onset primary dystonia in an African American family. Dr. Wszolek subsequently teamed up with an international group of researchers led by Mark LeDoux, MD, PhD. Their research resulted in a new paper published in Human Molecular Genetics that describes a previously unknown mutation in this family and three Caucasian families. Dr. LeDoux is a past DMRF grant recipient and former member of the Medical & Scientific Advisory Council.
The members of the African American family who participated in these studies were affected by cervical, laryngeal, and hand/forearm dystonias. After excluding mutations in known primary dystonia genes (TOR1A, THAP1, and CIZ1), whole-exome sequencing identified a unique mutation in the GNAL/DYT25 gene. Screening of 760 volunteers with primary dystonia identified the three Caucasian families who also exhibited GNAL mutations. These mutations show incomplete penetrance; not every person who has a mutation developed dystonia. These findings corroborate those of a recent study which identified GNAL mutations in Caucasian families of mixed European ancestry with mainly adult onset cervical and segmental dystonia.
This discovery provides another important insight into the dystonia mechanism, the opportunity for development of potential new treatment strategies, and increased visibility of the impact of dystonia in African American families.
The DMRF acknowledges all of the researchers who contributed to this study and the affected families and individuals who graciously participated.
Vemula SR, Puschmann A, Xiao J, Zhao Y, Rudziñska M, Frei KP, Truong DD, Wszolek ZK, Ledoux MS.
Source, “Role of Gα(olf) in Familial and Sporadic Adult-Onset Primary Dystonia” Hum Mol Genet. 2013 Feb 27.
To access the abstract go to: http://www.ncbi.nlm.nih.gov/pubmed/23449625