TY - JOUR
T1 - An African-American family with dystonia
AU - Puschmann, Andreas
AU - Xiao, Jianfeng
AU - Bastian, Robert W.
AU - Searcy, Jill A.
AU - LeDoux, Mark S.
AU - Wszolek, Zbigniew K.
N1 - Funding Information:
The authors wish to express their gratitude to all members of this family who participated in the study. We thank Audrey Strongosky, Mayo Clinic in Florida, for preparing the graphics of the pedigree ( Fig. 1 ). Andreas Puschmann received funding from the Swedish Parkinson Academy , AFA Insurance , The Swedish Parkinson Foundation , Apotekare Hedbergs Foundation , Elsa Schmitz Foundation , and Lund University Research Foundation . The Swedish Parkinson Academy, The Research Foundation of the Swedish Parkinson’s Disease Association, Lund University Research Fund, and The Royal Physiographic Society in Lund, Sweden. Mark S. LeDoux was supported by the Neuroscience Institute at the University of Tennessee Health Science Center, Dystonia Medical Research Foundation , NIH grants R01NS048458 and R01NS069936 , NIH U54 Dystonia Coalition (1U54NS065701) Pilot Projects Program, and the Parkinson’s & Movement Disorder Foundation . Zbigniew K. Wszolek is partially supported by the NIH/NINDS 1RC2NS070276 , NS057567 , P50NS072187 , Dystonia Medical Research Foundation, Mayo Clinic Florida (MCF) Research Committee CR programs ( MCF #90052030 and MCF #90052030 ), and the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch (MCF #90052031/PAU #90052).
PY - 2011/8
Y1 - 2011/8
N2 - The genetic cause of late-onset focal and segmental dystonia remains unknown in most individuals. Recently, mutations in Thanatos-associated protein domain containing, apoptosis associated protein 1 (THAP1) have been described in DYT6 dystonia and associated with some cases of familial and sporadic late-onset dystonia in Caucasians. We are not aware of any previous descriptions of familial dystonia in African-Americans or reports of THAP1 mutations in African-Americans. Herein, we characterize an African-American (AA) kindred with late-onset primary dystonia, clinically and genetically. The clinical phenotype included cervical, laryngeal and hand-forearm dystonia. Symptoms were severe and disabling for several family members, whereas others only displayed mild signs. There were no accompanying motor or cognitive signs. In this kindred, age of onset ranged from 45 to 50 years and onset was frequently sudden, with symptoms developing within weeks or months. DYT1 was excluded as the cause of dystonia in this kindred. The entire genomic region of THAP1, including non-coding regions, was sequenced. We identified 13 sequence variants in THAP1, although none co-segregated with dystonia. A novel THAP1 variant (c.-237-3G>T/A) was found in 3/84 AA dystonia patient alleles and 3/212 AA control alleles, but not in 5870 Caucasian alleles. In summary, although previously unreported, familial primary dystonia does occur in African-Americans. Genetic analysis of the entire genomic region of THAP1 revealed a novel variant that was specific for African-Americans. Therefore, genetic testing for dystonia and future studies of candidate genes must take genetic background into consideration.
AB - The genetic cause of late-onset focal and segmental dystonia remains unknown in most individuals. Recently, mutations in Thanatos-associated protein domain containing, apoptosis associated protein 1 (THAP1) have been described in DYT6 dystonia and associated with some cases of familial and sporadic late-onset dystonia in Caucasians. We are not aware of any previous descriptions of familial dystonia in African-Americans or reports of THAP1 mutations in African-Americans. Herein, we characterize an African-American (AA) kindred with late-onset primary dystonia, clinically and genetically. The clinical phenotype included cervical, laryngeal and hand-forearm dystonia. Symptoms were severe and disabling for several family members, whereas others only displayed mild signs. There were no accompanying motor or cognitive signs. In this kindred, age of onset ranged from 45 to 50 years and onset was frequently sudden, with symptoms developing within weeks or months. DYT1 was excluded as the cause of dystonia in this kindred. The entire genomic region of THAP1, including non-coding regions, was sequenced. We identified 13 sequence variants in THAP1, although none co-segregated with dystonia. A novel THAP1 variant (c.-237-3G>T/A) was found in 3/84 AA dystonia patient alleles and 3/212 AA control alleles, but not in 5870 Caucasian alleles. In summary, although previously unreported, familial primary dystonia does occur in African-Americans. Genetic analysis of the entire genomic region of THAP1 revealed a novel variant that was specific for African-Americans. Therefore, genetic testing for dystonia and future studies of candidate genes must take genetic background into consideration.
KW - Adult-onset dystonias
KW - African-American
KW - DYT6
KW - Dystonia
KW - Dystonia, Hereditary
KW - Focal dystonia
KW - Genetics
KW - THAP1
UR - http://www.scopus.com/inward/record.url?scp=79960209433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960209433&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2011.04.019
DO - 10.1016/j.parkreldis.2011.04.019
M3 - Article
C2 - 21601506
AN - SCOPUS:79960209433
SN - 1353-8020
VL - 17
SP - 547
EP - 550
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 7
ER -