scholarly journals Friedreich's Ataxia, Frataxin, PIP5K1B: Echo of a Distant Fracas

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Aurélien Bayot ◽  
Pierre Rustin
Keyword(s):  
Candidate Gene ◽  
Recent Observation ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
The Other ◽  
First Intron ◽  
Other Hand ◽  
Encoding Gene ◽  
Instrumental Role

“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). The instrumental role in the disease of large triplet expansions in the first intron ofFXNhas been thereafter fully confirmed, and this no longer suffers any dispute (Koeppen, 2011). On the other hand, a recent study suggests that the consequences of these large expansions inFXNare wider than previously thought and that the expression of surrounding genes, includingPIP5K1B, could be concurrently modulated by these large expansions (Bayot et al., 2013). This recent observation raises a number of important and yet unanswered questions for scientists and clinicians working on FRDA; these questions are the substratum of this paper.

scholarly journals Future Prospects of Gene Therapy for Friedreich’s Ataxia

2021 ◽  
Vol 22 (4) ◽  
pp. 1815 ◽  
Author(s):  
Gabriel Ocana-Santero ◽  
Javier Díaz-Nido ◽  
Saúl Herranz-Martín
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Autosomal Recessive ◽  
State Of The Art ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
First Intron ◽  
Progressive Neurodegeneration ◽  
Feasible Solutions ◽  
Neurogenetic Disease

Friedreich’s ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum. The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. Currently, there is no effective treatment to delay neurodegeneration in Friedreich’s ataxia. A plausible therapeutic approach is gene therapy. Indeed, Friedreich’s ataxia mouse models have been treated with viral vectors en-coding for either FXN or neurotrophins, such as brain-derived neurotrophic factor showing promising results. Thus, gene therapy is increasingly consolidating as one of the most promising therapies. However, several hurdles have to be overcome, including immunotoxicity and pheno-toxicity. We review the state of the art of gene therapy in Friedreich’s ataxia, addressing the main challenges and the most feasible solutions for them.

scholarly journals Electrophysiological Investigation of the Auditory System in Friedreich’s Ataxia

1982 ◽  
Vol 9 (2) ◽  
pp. 131-135 ◽  
Author(s):  
M.J. Taylor ◽  
J.B. McMenamin ◽  
E. Andermann ◽  
G.V. Watters
Keyword(s):  
Auditory System ◽  
Friedreich’S Ataxia ◽  
Auditory Brainstem ◽  
Friedreich's Ataxia ◽  
The Other ◽  
Auditory Brainstem Responses ◽  
Evoked Responses ◽  
Electrophysiological Investigation ◽  
Auditory Evoked Responses ◽  
Normal Controls

ABSTRACT:Auditory brainstem responses (ABRs) and cortical auditory evoked responses (AERs) were studied in a series of 16 Friedreich’s ataxia patients who varied in age, degree of clinical involvement and duration of the disorder. The ABRs were markedly abnormal in all but the youngest patient, and the abnormalities reflected the severity and duration of the disease. The latencies of the AERs were significantly longer in the Friedreich’s ataxia patients compared to normal controls, suggesting cortical as well as peripheral involvement of the auditory system. These data are discussed in terms of the neuropathology of the disorder and the similarities with the other sensory systems in Friedreich’s ataxia patients.

scholarly journals Reduced Formation of Hippuric Acid After Oral Benzoic Acid in Friedreich’s Ataxia

1982 ◽  
Vol 9 (2) ◽  
pp. 217-220
Author(s):  
A. Barbeau ◽  
R. Bouchard ◽  
T. Cloutier ◽  
J.P. Bouchard
Keyword(s):  
Benzoic Acid ◽  
Bile Acids ◽  
Normal Control ◽  
Hippuric Acid ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
The Other ◽  
Acid Load ◽  
Relationship Of ◽  
The Relationship

SUMMARY:We have observed a markedly decreased formation of hippuric acid after benzoic acid load in patients with typical Friedreich’s Ataxia compared to normal control subjects. Since there is evidence for normal or even enhanced tauro-conjugation in the bile of patients with this disease, with a decreased G/T ratio, it is unlikely that co-factor or enzyme concentrations are the cause of this defect. We postulate decreased availability of the enzyme for glycine conjugation either to bile acids in the usual situation or to benzoic acid in the artefactual test condition. This could be due to the enzyme’s preference for an increased amount of taurine substrate in the liver. The relationship of this observation to the other biochemical changes observed in Friedreich’s Ataxia must still be established.

scholarly journals Friedreich’s Ataxia: Clinical Presentation of a Compound Heterozygote Child with a Rare Nonsense Mutation and Comparison with Previously Published Cases

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Vamshi K. Rao ◽  
Christine J. DiDonato ◽  
Paul D. Larsen
Keyword(s):  
Point Mutation ◽  
Nonsense Mutation ◽  
Point Mutations ◽  
Friedreich’S Ataxia ◽  
Repeat Expansion ◽  
Friedreich's Ataxia ◽  
The Other ◽  
Compound Heterozygous ◽  
Compound Heterozygosity ◽  
Nonsense Mutations

Friedreich’s ataxia is a neurodegenerative disorder associated with a GAA trinucleotide repeat expansion in intron 1 of the frataxin (FXN) gene. It is the most common autosomal recessive cerebellar ataxia, with a mean age of onset at 16 years. Nearly 95-98% of patients are homozygous for a 90-1300 GAA repeat expansion with only 2-5% demonstrating compound heterozygosity. Compound heterozygous individuals have a repeat expansion in one allele and a point mutation/deletion/insertion in the other. Compound heterozygosity and point mutations are very rare causes of Friedreich’s ataxia and nonsense mutations are a further rarity among point mutations. We report a rare compound heterozygous Friedrich’s ataxia patient who was found to have one expanded GAA FXN allele and a nonsense point mutation in the other. We summarize the four previously published cases of nonsense mutations and compare the phenotype to that of our patient. We compared clinical information from our patient with other nonsense FXN mutations reported in the literature. This nonsense mutation, to our knowledge, has only been described once previously; interestingly the individual was also of Cuban ancestry. A comparison with previously published cases of nonsense mutations demonstrates some common clinical characteristics.

scholarly journals Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chiranjeevi Sandi ◽  
Sahar Al-Mahdawi ◽  
Mark A. Pook
Keyword(s):  
Autosomal Recessive ◽  
Trinucleotide Repeat ◽  
Neurodegenerative Disorder ◽  
Therapeutic Option ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Epigenetic Changes ◽  
First Intron ◽  
Challenges And Opportunities ◽  
Transcriptional Reactivation

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by homozygous expansion of a GAA·TTC trinucleotide repeat within the first intron of the FXN gene, leading to reduced FXN transcription and decreased levels of frataxin protein. Recent advances in FRDA research have revealed the presence of several epigenetic modifications that are either directly or indirectly involved in this FXN gene silencing. Although epigenetic marks may be inherited from one generation to the next, modifications of DNA and histones can be reversed, indicating that they are suitable targets for epigenetic-based therapy. Unlike other trinucleotide repeat disorders, such as Huntington disease, the large expansions of GAA·TTC repeats in FRDA do not produce a change in the frataxin amino acid sequence, but they produce reduced levels of normal frataxin. Therefore, transcriptional reactivation of the FXN gene provides a good therapeutic option. The present paper will initially focus on the epigenetic changes seen in FRDA patients and their role in the silencing of FXN gene and will be concluded by considering the potential epigenetic therapies.

scholarly journals Genotypic Markers of Yersinia Enterocolitica O:9 Isolated from Cows Positive in Serological Examination for Bovine Brucellosis

2012 ◽  
Vol 56 (4) ◽  
pp. 479-482
Author(s):  
Marcin Weiner ◽  
Krzysztof Szulowski ◽  
Wojciech Iwaniak ◽  
Jolanta Złotnicka
Keyword(s):  
Molecular Markers ◽  
Yersinia Enterocolitica ◽  
False Positive ◽  
The Other ◽  
Bovine Brucellosis ◽  
Serological Examination ◽  
Other Hand ◽  
Encoding Gene ◽  
Almost All

Abstract The aim of the study was to perform a molecular investigations for the presence of pathogenicity genotypic markers of Y.enterocolitica O:9 isolated from cattle, in which initially positive serological reactions for brucellosis were observed. Almost all isolates were ail-, ystA- and myfA-positive (n=19). On the other hand, one isolate, which harboured plasmid encoding gene yadA was ail- , ystA- and myfA-negative. The plasmid encoding yadA marker was present in half of the isolates tested. None of the examined isolates was ystB-positive. The results of the investigations revealed that the Y. enterocolitica O:9 isolates, related to false positive serological results for brucellosis, may be also potentially pathogenic for humans, due to the presence of chromosomal and plasmidencoded molecular markers.

scholarly journals Generation of transgene-free iPSC lines from three patients with Friedreich’s ataxia (FRDA) carrying GAA triplet expansions in the first intron of FXN gene

2021 ◽  
pp. 102438
Author(s):  
Simge Kelekçi ◽  
Deniz Uğurlu-Çimen ◽  
Deniz Ata ◽  
Burcu Özçimen ◽  
Abdullah Burak Yıldız ◽  
...  
Keyword(s):  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
First Intron

A study of cometary eruptions through OH radio-lines

1999 ◽  
Vol 173 ◽  
pp. 249-254
Author(s):  
A.M. Silva ◽  
R.D. Miró
Keyword(s):  
Short Duration ◽  
Growth Curves ◽  
The Other ◽  
Initial Mass ◽  
Radio Lines ◽  
Other Hand ◽  
Sudden Rise

AbstractWe have developed a model for theH2OandOHevolution in a comet outburst, assuming that together with the gas, a distribution of icy grains is ejected. With an initial mass of icy grains of 108kg released, theH2OandOHproductions are increased up to a factor two, and the growth curves change drastically in the first two days. The model is applied to eruptions detected in theOHradio monitorings and fits well with the slow variations in the flux. On the other hand, several events of short duration appear, consisting of a sudden rise ofOHflux, followed by a sudden decay on the second day. These apparent short bursts are frequently found as precursors of a more durable eruption. We suggest that both of them are part of a unique eruption, and that the sudden decay is due to collisions that de-excite theOHmaser, when it reaches the Cometopause region located at 1.35 × 105kmfrom the nucleus.

Closing the GAP—A 5Å Scanning Microscope

1969 ◽  
Vol 27 ◽  
pp. 6-7
Author(s):  
A. V. Crewe
Keyword(s):  
Normal Form ◽  
The Other ◽  
Resolving Power ◽  
Scanning Microscope ◽  
Conventional Microscope ◽  
Other Hand ◽  
Closing The Gap ◽  
Thermal Sources ◽  
Better Than ◽  
Transmission Microscope

We have become accustomed to differentiating between the scanning microscope and the conventional transmission microscope according to the resolving power which the two instruments offer. The conventional microscope is capable of a point resolution of a few angstroms and line resolutions of periodic objects of about 1Å. On the other hand, the scanning microscope, in its normal form, is not ordinarily capable of a point resolution better than 100Å. Upon examining reasons for the 100Å limitation, it becomes clear that this is based more on tradition than reason, and in particular, it is a condition imposed upon the microscope by adherence to thermal sources of electrons.

Life Beyond 1MeV

1980 ◽  
Vol 38 ◽  
pp. 30-33
Author(s):  
K.H. Westmacott
Keyword(s):  
Electron Microscopy ◽  
Past Experience ◽  
The Other ◽  
Good Case ◽  
Other Hand ◽  
The U.S

Life beyond 1MeV – like life after 40 – is not too different unless one takes advantage of past experience and is receptive to new opportunities. At first glance, the returns on performing electron microscopy at voltages greater than 1MeV diminish rather rapidly as the curves which describe the well-known advantages of HVEM often tend towards saturation. However, in a country with a significant HVEM capability, a good case can be made for investing in instruments with a range of maximum accelerating voltages. In this regard, the 1.5MeV KRATOS HVEM being installed in Berkeley will complement the other 650KeV, 1MeV, and 1.2MeV instruments currently operating in the U.S. One other consideration suggests that 1.5MeV is an optimum voltage machine – Its additional advantages may be purchased for not much more than a 1MeV instrument. On the other hand, the 3MeV HVEM's which seem to be operated at 2MeV maximum, are much more expensive.

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