Prevalence of <i>THAP1</i> sequence variants in German patients with primary dystonia

Sohn, A.; Glöckle, Nicola; Doetzer, Andrea Duarte; Deuschl, Günther; Felbor, Ute; Topka, Helge; Schöls, Lüdger; Rieß, Olaf; Bauer, Peter; Müller, Ulrich; Grundmann, Kathrin

doi:10.1002/mds.23207

Cited by 32 publications

(42 citation statements)

References 16 publications

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“…Mutation frequency in the literature ranges from about 0.5-1.8% for mainly unselected primary dystonia patients. [9][10][11][12][13]15 Thus, THAP1 mutations are rare in dystonia patients. About 50 different THAP1 mutations have been reported to date.…”

Section: Discussionmentioning

confidence: 99%

“…About 50 different THAP1 mutations have been reported to date. 2,[6][7][8][9][10][11][12][13][14][15][16][17]22 One-third of the mutations represents missense mutations located in the THAP domain and is thought to interrupt DNA binding. Another one-third of the mutations are considered to disturb the NLS, such as nonsense mutations, small insertions/deletions, or missense mutations within the NLS.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9][10][11][12][13][14][15] In more than 80% of the patients dystonia spreads to other body parts. Speech was affected in about 70% of patients.…”

Section: Discussionmentioning

confidence: 99%

“…5 About 50 different THAP1 mutations have been reported to date including missense, nonsense, and frameshift mutations. 2,[6][7][8][9][10][11][12][13][14][15][16][17] In addition to the disease-causing mutations, two variants, c.-237_236delinsTT and c.71+9C4A, in the non-coding region of THAP1 may be associated with dystonia. 9,13 DYT6 typically manifests as early-onset generalized or segmental dystonia, frequently with prominent laryngeal involvement and a rostrocaudal evolution of symptoms.…”

Section: Introductionmentioning

confidence: 99%

“…9,13 DYT6 typically manifests as early-onset generalized or segmental dystonia, frequently with prominent laryngeal involvement and a rostrocaudal evolution of symptoms. [6][7][8][9][10][11][12][13][14][15] The phenotype though is highly variable even within a single family ranging from unaffected carriers to generalized dystonia. 8,9,13 Mutation frequency varies between 0.5% in unselected primary dystonia patients 13 and 25% in non-DYT1 multiplex families in whom at least one individual had non-focal involvement and onset of symptoms by o 22 years.…”

Section: Introductionmentioning

confidence: 99%

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Identification and functional analysis of novel THAP1 mutations

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9][10][11][12][13][14][15] In more than 80% of the patients dystonia spreads to other body parts. Speech was affected in about 70% of patients.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification and functional analysis of novel THAP1 mutations

et al. 2011

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Deleterious Effects of Beta-Blockers on Survival in Patients With Cirrhosis and Refractory Ascites†,‡

Mélot²,

et al. 2010

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Beta-blockers may have a negative impact on survival in patients with cirrhosis and refractory ascites. The aim of this study was to evaluate the effect of the administration of betablockers on long-term survival in patients with cirrhosis and refractory ascites. We performed a single-center, observational, case-only, prospective study of patients with cirrhosis and refractory ascites who did or did not receive beta-blockers for the prevention of gastrointestinal bleeding; 151 patients were included. The mean Model for End-Stage Liver Disease score was 18.8 6 4.1. All patients regularly underwent large-volume paracentesis and intravenous albumin administration. Seventy-seven patients (51%) were treated with propranolol (113 6 46 mg/day). The median follow-up for the whole group was 8 months. The median survival time was 10 months [95% confidence interval (CI) 5 8-12 months]. The probability of survival at 1 year was 41% (95% CI 5 33%-49%). The clinical characteristics and laboratory values at enrolment were not significantly different between patients who were receiving propranolol and those who were not. The median survival time was 20.0 months (95% CI 5 4.8-35.2 months) in patients not treated with propranolol and 5.0 months (95% CI 5 3.5-6.5 months) in those treated with propranolol (P 5 0.0001). The 1-year probability of survival was significantly lower in patients who received propranolol [19% (95% CI 5 9%-29%)] versus those who did not [64% (95% CI 5 52%-76%), P < 0.0001]. The independent variables of mortality were Child-Pugh class C, hyponatremia and renal failure as causes of refractory ascites, and beta-blocker therapy. Conclusion: The use of beta-blockers is associated with poor survival in patients with refractory ascites. These results suggest that betablockers should be contraindicated in these patients.

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DYT6 dystonia: Review of the literature and creation of the UMD locus-specific database (LSDB) for mutations in the THAP1 gene

Blanchard

Roubertie

et al. 2011

Hum. Mutat.

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By family-based screening, first Fuchs and then many other authors showed that mutations in THAP1 (THAP [thanatos-associated protein] domain-containing, apoptosis-associated protein 1) account for a substantial proportion of familial, early-onset, nonfocal, primary dystonia cases (DYT6 dystonia). THAP1 is the first transcriptional factor involved in primary dystonia and the hypothesis of a transcriptional deregulation, which was primarily proposed for the X-linked dystonia-parkinsonism (DYT3 dystonia), provided thus a new way to investigate the possible mechanism underlying the development of dystonic movements. Currently, 56 families present with a THAP1 mutation; however, no genotype/phenotype relationship has been found. Therefore, we carried out a systematic review of the literature on the THAP1 gene to colligate all reported patients with a specific THAP1 mutation and the associated clinical signs in order to describe the broad phenotypic continuum of this disorder. To facilitate the comparison of the identified mutations, we created a Locus-Specific Database (UMD-THAP1 LSDB) available at http://www.umd.be/THAP1/. Currently, the database lists 56 probands and 43 relatives with the associated clinical phenotype when available. The identification of a larger number of THAP1 mutations and collection of high-quality clinical information for each described mutation through international collaborative effort will help investigating the structure-function and genotype-phenotype correlations in DYT6 dystonia.

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Prevalence of THAP1 sequence variants in German patients with primary dystonia

Cited by 32 publications

References 16 publications

Identification and functional analysis of novel THAP1 mutations

Identification and functional analysis of novel THAP1 mutations

Deleterious Effects of Beta-Blockers on Survival in Patients With Cirrhosis and Refractory Ascites†,‡

DYT6 dystonia: Review of the literature and creation of the UMD locus-specific database (LSDB) for mutations in the THAP1 gene

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