Dataset Information

Novel THAP1 sequence variants in primary dystonia.

ABSTRACT: 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.To examine a large cohort of subjects with mainly adult-onset primary dystonia for sequence variants in THAP1.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.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).A heterogeneous collection of THAP1 sequence variants is associated with varied anatomical distributions and onset ages of both familial and sporadic primary dystonia.

SUBMITTER: Xiao J

PROVIDER: S-EPMC2809032 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel THAP1 sequence variants in primary dystonia.

Xiao J J Zhao Y Y Bastian R W RW Perlmutter J S JS Racette B A BA Tabbal S D SD Karimi M M Paniello R C RC Wszolek Z K ZK Uitti R J RJ Van Gerpen J A JA Simon D K DK Tarsy D D Hedera P P Truong D D DD Frei K P KP Dev Batish S S Blitzer A A Pfeiffer R F RF Gong S S LeDoux M S MS

Neurology 20100101 3

<h4>Background</h4>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.<h4>Objective</h4>To examine a large cohort of subjects with mainly adult-onset primary dystonia fo ...[more]

PMID: 20083799

Similar Datasets

Project description:The aim of this study was to assess the presence of DYT6 mutations in Polish patients with isolated dystonia and to characterize their phenotype. We sequenced THAP1 exons 1, 2 and 3 including exon-intron boundaries and 5'UTR fragment in 96 non-DYT1 dystonia patients. In four individuals single nucleotide variations were identified. The coding substitutions were: c. 238A>G (p.Ile80Val), found in two patients, and c.167A>G (p.Glu56Gly), found in one patient. The same variations were present also in the patients' symptomatic as well as asymptomatic relatives. Mutation penetration in the analyzed families was 50-66.7%. In the fourth patient, a novel c.-249C>A substitution in the promoter region was identified. The patient, initially suspected of idiopathic isolated dystonia, finally presented with pantothenate kinase 2-associated neurodegeneration phenotype and was a carrier of two PANK2 mutations. This is the first identified NBIA1 case carrying mutations in both PANK2 and THAP1 genes. In all symptomatic THAP1 mutation carriers (four probands and their three affected relatives) the first signs of dystonia occurred before the age of 23. A primary localization typical for DYT6 dystonia was observed in six individuals. Five subjects developed the first signs of dystonia in the upper limb. In one patient the disease began from laryngeal involvement. An uncommon primary involvement of lower limb was noted in the THAP1 and PANK2 mutations carrier. Neither of these THAP1 substitutions were found in 150 unrelated healthy controls. To the contrary, we identified a heterozygous C/T genotype of c.57C>T single nucleotide variation (p.Pro19Pro, rs146087734) in one healthy control, but in none of the patients. Therefore, a previously proposed association between this substitution and DYT6 dystonia seems unlikely. We found also no significant difference between cases and controls in genotypes distribution of the two-nucleotide -237-236 GA>TT (rs370983900 & rs1844977763) polymorphism.

Dataset Information

Novel THAP1 sequence variants in primary dystonia.

Publications

Novel THAP1 sequence variants in primary dystonia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets