Molecular dynamics simulations are used to elucidate the structure and thermodynamics of DNA triplexes associated with the neurodegenerative disease Friedreich's ataxia (FRDA), as well as complexes of these triplexes with the small molecule netropsin, which is known to destabilise triplexes.
Friedreich's ataxia (FRDA), the most common subtype of early onset hereditary spinocerebellar ataxia (SCA), is an autosomal recessive neurodegenerative disorder caused by unstable GAA tri-nucleotide expansions in the first intron of FRDA gene located at 9q13-q21.1 position.
The DNA abnormality found in 98% of Friedreich's ataxia (FRDA) patients is the unstable hyperexpansion of a GAA.TTC triplet repeat in the first intron of the frataxin gene.
Friedreich ataxia (FRDA), a progressive neurodegenerative disease, is due to the partial loss of function of frataxin, a mitochondrial protein of unknown function.
FRDA is usually due to homozygosity for trinucleotide GAA repeat expansions found within first intron of the FRATAXIN (FXN) gene, which results in reduced levels of the mitochondrial protein FXN.
A specific pyrrole-imidazole polyamide targeting GAA·TTC triplet-repeat DNA partially blocked repeat expansion by displacing MSH2 from FXN intron 1 in FRDA iPSCs.
Expansion of GAA·TTC repeats within the first intron of the frataxin gene is the cause of Friedreich's ataxia (FRDA), an autosomal recessive neurodegenerative disorder.
Here biochemical and structural properties of FXN variants, including three FRDA missense mutations (N146K, Q148R, and R165C) and three related mutants (N146A, Q148G, and Q153A), were determined in an effort to understand the structural basis for the loss of function.
The onset and progress of Friedreich's ataxia (FRDA) is associated with the genetic instability of the (GAA).(TTC) trinucleotide repeats located within the frataxin gene.
We investigated the effects of FRDA on regional long axis function of the left and right ventricles, and also the relationship of long axis systolic (s`) and early diastolic (e`) peak velocities with GAA repeat number on the shorter (GAA1) and longer FXN alleles (GAA2).
These cases, and a further five reported cases of point mutations causing FRDA, demonstrate that splicing, nonsense, or initiation codon mutations (which cause a complete absence of functional frataxin) are associated with a severe phenotype.
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition with a heterogeneous cardiac phenotype caused primarily by an expanded GAA trinucleotide repeat in the frataxin gene (FXN).
The effects of stably transfected FAST-1 expression on CTCF occupancy and heterochromatin formation at the FXN locus suggest a direct role for FAST-1 in the FRDA molecular disease mechanism.
A GAA-repeat in the X25 gene is causing Friedreich's ataxia (FRDA), a common neurodegenerative disease and >20% of FRDA patients develop type II diabetes (T2D).
"Frataxin fracas" were the words used when referring to the frataxin-encoding gene (FXN) burst in as a motive to disqualify an alternative candidate gene, PIP5K1B, as an actor in Friedreich's ataxia (FRDA) (Campuzano et al., 1996; Cossee et al., 1997; Carvajal et al., 1996).
Friedreich's ataxia (FRDA), the most common inherited ataxia, is associated with an unstable expansion of GAA repeats in the first intron of the frataxin gene on chromosome 9.
These cases, and a further five reported cases of point mutations causing FRDA, demonstrate that splicing, nonsense, or initiation codon mutations (which cause a complete absence of functional frataxin) are associated with a severe phenotype.
Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease, is associated with an unstable expansion of a GAA trinucleotide repeat in the first intron of the frataxin gene on chromosome 9q13.
Friedreich Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder most commonly caused by guanine-adenine-adenine (GAA) trinucleotide repeat expansions in both alleles of the FXN gene.
Here we describe a neuronal cell model for FRDA based on the use of lentiviral vectors that carry minigenes encoding frataxin-specific shRNAs that silence the expression of this gene.