Identification and functional analysis of novel THAP1 mutations.
Standard
Identification and functional analysis of novel THAP1 mutations. / Lohmann, Katja; Uflacker, Nils; Erogullari, Alev; Lohnau, Thora; Winkler, Susen; Dendorfer, Andreas; Schneider, Susanne A; Osmanovic, Alma; Svetel, Marina; Ferbert, Andreas; Zittel, Simone; Kühn, Andrea A; Schmidt, Alexander; Altenmüller, Eckart; Münchau, Alexander; Kamm, Christoph; Wittstock, Matthias; Kupsch, Andreas; Moro, Elena; Volkmann, Jens; Kostic, Vladimir; Kaiser, Frank J; Klein, Christine; Brüggemann, Norbert.
in: EUR J HUM GENET, Jahrgang 20, Nr. 2, 2, 2012, S. 171-175.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Identification and functional analysis of novel THAP1 mutations.
AU - Lohmann, Katja
AU - Uflacker, Nils
AU - Erogullari, Alev
AU - Lohnau, Thora
AU - Winkler, Susen
AU - Dendorfer, Andreas
AU - Schneider, Susanne A
AU - Osmanovic, Alma
AU - Svetel, Marina
AU - Ferbert, Andreas
AU - Zittel, Simone
AU - Kühn, Andrea A
AU - Schmidt, Alexander
AU - Altenmüller, Eckart
AU - Münchau, Alexander
AU - Kamm, Christoph
AU - Wittstock, Matthias
AU - Kupsch, Andreas
AU - Moro, Elena
AU - Volkmann, Jens
AU - Kostic, Vladimir
AU - Kaiser, Frank J
AU - Klein, Christine
AU - Brüggemann, Norbert
PY - 2012
Y1 - 2012
N2 - Mutations in THAP1 have been associated with dystonia 6 (DYT6). THAP1 encodes a transcription factor that represses the expression of DYT1. To further evaluate the mutational spectrum of THAP1 and its associated phenotype, we sequenced THAP1 in 567 patients with focal (n = 461), segmental (n = 68), or generalized dystonia (n = 38). We identified 10 novel variants, including six missense substitutions within the DNA-binding Thanatos-associated protein domain (Arg13His, Lys16Glu, His23Pro, Lys24Glu, Pro26Leu, Ile80Val), a 1bp-deletion downstream of the nuclear localization signal (Asp191Thrfs*9), and three alterations in the untranslated regions. The effect of the missense variants was assessed using prediction tools and luciferase reporter gene assays. This indicated the Ile80Val substitution as a benign variant. The subcellular localization of Asp191Thrfs*9 suggests a disturbed nuclear import for this mutation. Thus, we consider six of the 10 novel variants as pathogenic mutations accounting for a mutation frequency of 1.1%. Mutation carriers presented mainly with early onset dystonia (
AB - Mutations in THAP1 have been associated with dystonia 6 (DYT6). THAP1 encodes a transcription factor that represses the expression of DYT1. To further evaluate the mutational spectrum of THAP1 and its associated phenotype, we sequenced THAP1 in 567 patients with focal (n = 461), segmental (n = 68), or generalized dystonia (n = 38). We identified 10 novel variants, including six missense substitutions within the DNA-binding Thanatos-associated protein domain (Arg13His, Lys16Glu, His23Pro, Lys24Glu, Pro26Leu, Ile80Val), a 1bp-deletion downstream of the nuclear localization signal (Asp191Thrfs*9), and three alterations in the untranslated regions. The effect of the missense variants was assessed using prediction tools and luciferase reporter gene assays. This indicated the Ile80Val substitution as a benign variant. The subcellular localization of Asp191Thrfs*9 suggests a disturbed nuclear import for this mutation. Thus, we consider six of the 10 novel variants as pathogenic mutations accounting for a mutation frequency of 1.1%. Mutation carriers presented mainly with early onset dystonia (
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Adolescent
KW - Young Adult
KW - Polymorphism, Genetic
KW - Child
KW - Child, Preschool
KW - Genotype
KW - Protein Transport
KW - Age of Onset
KW - Gene Frequency
KW - Genetic Association Studies
KW - Mutation
KW - Apoptosis Regulatory Proteins/genetics/metabolism
KW - DNA-Binding Proteins/genetics/metabolism
KW - Dystonia/epidemiology/genetics/metabolism
KW - Nuclear Proteins/genetics/metabolism
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Adolescent
KW - Young Adult
KW - Polymorphism, Genetic
KW - Child
KW - Child, Preschool
KW - Genotype
KW - Protein Transport
KW - Age of Onset
KW - Gene Frequency
KW - Genetic Association Studies
KW - Mutation
KW - Apoptosis Regulatory Proteins/genetics/metabolism
KW - DNA-Binding Proteins/genetics/metabolism
KW - Dystonia/epidemiology/genetics/metabolism
KW - Nuclear Proteins/genetics/metabolism
M3 - SCORING: Journal article
VL - 20
SP - 171
EP - 175
JO - EUR J HUM GENET
JF - EUR J HUM GENET
SN - 1018-4813
IS - 2
M1 - 2
ER -