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An African-American family with dystonia.

Puschmann, Andreas LU ; Xiao, Jianfeng; Bastian, Robert W; Searcy, Jill A; Ledoux, Mark S and Wszolek, Zbigniew K (2011) In Parkinsonism & Related Disorders 17. p.547-550
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Parkinsonism & Related Disorders
volume
17
pages
547 - 550
publisher
Elsevier
external identifiers
  • wos:000293728300009
  • pmid:21601506
  • scopus:79960209433
ISSN
1873-5126
DOI
10.1016/j.parkreldis.2011.04.019
language
English
LU publication?
yes
id
378ffa4e-09c4-4b48-94a5-9a27b9c1c26d (old id 1972274)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21601506?dopt=Abstract
date added to LUP
2011-06-07 21:57:18
date last changed
2017-02-12 04:19:29
@article{378ffa4e-09c4-4b48-94a5-9a27b9c1c26d,
  abstract     = {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.},
  author       = {Puschmann, Andreas and Xiao, Jianfeng and Bastian, Robert W and Searcy, Jill A and Ledoux, Mark S and Wszolek, Zbigniew K},
  issn         = {1873-5126},
  language     = {eng},
  pages        = {547--550},
  publisher    = {Elsevier},
  series       = {Parkinsonism & Related Disorders},
  title        = {An African-American family with dystonia.},
  url          = {http://dx.doi.org/10.1016/j.parkreldis.2011.04.019},
  volume       = {17},
  year         = {2011},
}