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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Novel THAP1 sequence variants in primary dystonia
Neurology, Volume 74, No. 3, Year 2010
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Description
BACKGROUND: THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger domain and regulates cell proliferation. An exon 2 insertion/deletion frameshift mutation in THAP1 is responsible for DYT6 dystonia in Amish-Mennonites. Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence variants in non-Amish subjects. OBJECTIVE: To examine a large cohort of subjects with mainly adult-onset primary dystonia for sequence variants in THAP1. METHODS: With high-resolution melting, all 3 THAP1 exons were screened for sequence variants in 1,114 subjects with mainly adult-onset primary dystonia, 96 with unclassified dystonia, and 600 controls (400 neurologically normal and 200 with Parkinson disease). In addition, all 3 THAP1 exons were sequenced in 200 subjects with dystonia and 200 neurologically normal controls. RESULTS: Nine unique melting curves were found in 19 subjects from 16 families with primary dystonia and 1 control. Age at dystonia onset ranged from 8 to 69 years (mean 48 years). Sequencing identified 6 novel missense mutations in conserved regions of THAP1 (G9C [cervical, masticatory, arm], D17G [cervical], F132S [laryngeal], I149T [cervical and generalized], A166T [laryngeal], and Q187K [cervical]). One subject with blepharospasm and another with laryngeal dystonia harbored a c.-42C>T variant. A c.57C>T silent variant was found in 1 subject with segmental craniocervical dystonia. An intron 1 variant (c.71+9C>A) was present in 7 subjects with dystonia (7/1,210) but only 1 control (1/600). CONCLUSIONS: A heterogeneous collection of THAP1 sequence variants is associated with varied anatomical distributions and onset ages of both familial and sporadic primary dystonia. Copyright © 2010 by AAN Enterprises, Inc.
Authors & Co-Authors
Bastian, Robert W.
United States, Memphis
University of Tennessee Health Science Center
Perlmutter, Joel S.
United States, St. Louis
Washington University School of Medicine in St. Louis
Racette, Brad A.
United States, St. Louis
Washington University School of Medicine in St. Louis
Tabbal, Samer D.
United States, St. Louis
Washington University School of Medicine in St. Louis
Wszołek, Zbigniew K.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Uitti, Ryan J.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Statistics
Citations: 111
Authors: 6
Affiliations: 6
Identifiers
Doi:
10.1212/WNL.0b013e3181ca00ca
ISSN:
00283878
Research Areas
Cancer
Genetics And Genomics
Study Design
Cohort Study