Frataxin gene study in Friedreich ataxia disease: serum levels and environmental pollutants in purified water from a family in Sahuayo city at Michoacan State, Mexico in 2015

2016 ◽  
Vol 2016 (1) ◽  
Author(s):  
Maria-Elena Soto* ◽  
Alejandro Molina-Garcia* ◽  
Ingrid Flandes ◽  
Ricardo Marquez ◽  
Antonio Arias-Godinez ◽  
...  
Keyword(s):  
Friedreich Ataxia ◽  
Environmental Pollutants ◽  
Serum Levels ◽  
Gene Study ◽  
Frataxin Gene

Frataxin gene point mutations in Italian Friedreich ataxia patients

Neurogenetics ◽  
2007 ◽  
Vol 8 (4) ◽  
pp. 289-299 ◽  
Author(s):  
Cinzia Gellera ◽  
Barbara Castellotti ◽  
Caterina Mariotti ◽  
Rossana Mineri ◽  
Viviana Seveso ◽  
...  
Keyword(s):  
Friedreich Ataxia ◽  
Point Mutations ◽  
Frataxin Gene

scholarly journals Malaysian Siblings with Friedreich Ataxia and Chorea: A Novel Deletion in the Frataxin Gene

2004 ◽  
Vol 31 (3) ◽  
pp. 383-386 ◽  
Author(s):  
Siân D. Spacey ◽  
Blazej I. Szczygielski ◽  
Sean P. Young ◽  
Juliette Hukin ◽  
Kathy Selby ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Middle Eastern ◽  
Friedreich Ataxia ◽  
Hospital Setting ◽  
Southeast Asian ◽  
The Other ◽  
University Hospital ◽  
Compound Heterozygotes ◽  
Gaa Expansion ◽  
Frataxin Gene

Background:Friedrich ataxia (FRDA1) is most often the result of a homozygous GAA repeat expansion in the first intron of the frataxin gene (FRDA gene). This condition is seen in individuals of European, North African, Middle Eastern and Indian descent and has not been reported in Southeast Asian populations. Approximately 4% of FRDA1 patients are compound heterozygotes. These patients have a GAA expansion on one allele and a point mutation on the other and have been reported to have an atypical phenotype.Objective:To describe a novel dinucleotide deletion in the FRDA gene in two Malaysian siblings with FRDA1.Setting:Tertiary referral university hospital setting. Patients andMethods:A previously healthy 10-year-old Malaysian boy, presented with fever, lethargy, headaches, dysarthria, dysphagia, vertigo and ataxia which developed over a one week period. His neurological exam revealed evidence of dysarthria and ataxia, mild generalized weakness and choreoform movements of the tongue and hands. His reflexes were absent and Babinski sign was present bilaterally. A nine-year-old sister was found to have mild ataxia but was otherwise neurologically intact.Results:Molecular genetic studies demonstrated that both siblings were compound heterozygotes with a GAA expansion on one allele and a novel dinucleotide deletion on the other allele.Conclusion:We describe a novel dinucleotide deletion in the first exon of the FRDA gene in two siblings with FRDA1. Additionally this is the first report of FRDA1 occurring in a family of southeast Asian descent, it demonstrates intrafamilial phenotypic variability, and confirms that atypical phenotypes are associated with compound heterozygosity.

scholarly journals Dietary Fiber Reduces the Concentrations of Certain Aldehydes in Serum

2021 ◽  
Author(s):  
Shi Shi ◽  
Qingqing Zhu ◽  
Shengen Liao ◽  
Xu Zhu ◽  
Xiaosu Tang ◽  
...  
Keyword(s):  
Dietary Fiber ◽  
Sex Education ◽  
Smoking Status ◽  
Environmental Pollutants ◽  
Positive Association ◽  
Fold Increase ◽  
Serum Levels ◽  
Fiber Intake ◽  
Dietary Fiber Intake ◽  
Strong Negative Association

Abstract Aldehydes have been shown to be potentially carcinogenic, mutagenic, and cardiotoxic to humans. Dietary fiber reduces exposure to certain environmental pollutants and has been widely used to improve various metabolic disorders. However, the effects of dietary fiber on serum concentrations of aldehydes remain unexplored. We collected data from the National Health and Nutrition Examination Survey (NHANES) 2013–2014. Generalized linear regression and restricted cubic spline models were performed to elucidate the association of dietary fiber intake with the serum concentration of aldehydes. After fully adjusting for age, sex, education level, race, smoking status, alcohol use, diabetes, hypertension, body mass index, energy intake, poverty-income ratio and physical activity, dietary fiber intake had a strong negative association with serum levels of isopentanaldehyde and propanaldehyde and a positive association with serum levels of benzaldehyde. The estimated increases in the mean log2-unit (ng/mL) of aldehydes for each fold increase in dietary fiber ranged from − 0.155 (95% confidence intervals [CI]: -0.210 to -0.101) for isopentanaldehyde to -0.053 (95% CI: -0.094 to -0.011) for propanaldehyde and 0.156 (95% CI: 0.091 to 0.222) for benzaldehyde. No significant association was observed between dietary fiber intake and the concentration of any other aldehydes. These results demonstrate that dietary fiber reduces the concentration of certain aldehydes in serum.

scholarly journals The Role of Serum Levels of Neurofilament Light (NfL) Chain as a Biomarker in Friedreich Ataxia

2021 ◽  
Vol 15 ◽  
Author(s):  
Bernice Frempong ◽  
Robert B. Wilson ◽  
Kimberly Schadt ◽  
David R. Lynch
Keyword(s):  
Friedreich Ataxia ◽  
Serum Levels ◽  
Neurofilament Light

DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients

2008 ◽  
Vol 45 (12) ◽  
pp. 808-812 ◽  
Author(s):  
I Castaldo ◽  
M Pinelli ◽  
A Monticelli ◽  
F Acquaviva ◽  
M Giacchetti ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Age Of Onset ◽  
Friedreich Ataxia ◽  
Repeat Length ◽  
Intron 1 ◽  
Frataxin Gene

scholarly journals The Spectrum of Left Ventricular Changes in Friedreich Ataxia—Relation to Age and GAA Repeats in the Frataxin Gene

2012 ◽  
Vol 21 ◽  
pp. S273
Author(s):  
G. Romanelli ◽  
M. Delatycki ◽  
L. Donelan ◽  
R. Hassam ◽  
L. Corben ◽  
...  
Keyword(s):  
Friedreich Ataxia ◽  
Left Ventricular ◽  
Gaa Repeats ◽  
Frataxin Gene

scholarly journals Childhood Ataxia

2012 ◽  
Vol 27 (9) ◽  
pp. 1095-1120 ◽  
Author(s):  
Claire N. Ashley ◽  
Kelly D. Hoang ◽  
David R. Lynch ◽  
Susan L. Perlman ◽  
Bernard L. Maria
Keyword(s):  
Clinical Trials ◽  
Autosomal Recessive ◽  
Friedreich Ataxia ◽  
Chromosome 9 ◽  
Society Meeting ◽  
Natural History Study ◽  
Impaired Balance ◽  
Gaa Repeat Expansion ◽  
Childhood Ataxia ◽  
Frataxin Gene

Childhood ataxia is characterized by impaired balance and coordination primarily because of cerebellar dysfunction. Friedreich ataxia, a form of childhood ataxia, is the most common multisystem autosomal recessive disease. Most of these patients are homozygous for the GAA repeat expansion located on the first intron of the frataxin gene on chromosome 9. Mutations in the frataxin gene impair mitochondrial function, increase reactive oxygen species, and trigger redistribution of iron in the mitochondria and cytosol. Targeted therapies for Friedreich ataxia are undergoing testing. In addition, a centralized database, patient registry, and natural history study have been launched to support clinical trials in Friedreich ataxia. The 2011 Neurobiology of Disease in Children symposium, held in conjunction with the 40th annual Child Neurology Society meeting, aimed to (1) describe clinical features surrounding Friedreich ataxia, including cardiomyopathy and genetics; (2) discuss recent advances in the understanding of the pathogenesis of Friedreich ataxia and developments of clinical trials; (3) review new investigations of characteristic symptoms; and (4) establish clinical and biochemical overlaps in neurodegenerative diseases and possible directions for future basic, translational, and clinical studies.

A Drosophila model of Friedreich ataxia with CRISPR/Cas9 insertion of GAA repeats in the frataxin gene reveals in vivo protection by N-acetyl cysteine

2020 ◽  
Vol 29 (17) ◽  
pp. 2831-2844 ◽  
Author(s):  
Maria Russi ◽  
Elodie Martin ◽  
Benoit D’Autréaux ◽  
Laura Tixier ◽  
Hervé Tricoire ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Friedreich Ataxia ◽  
Progressive Increase ◽  
Therapeutic Interventions ◽  
Drosophila Model ◽  
Acetyl Cysteine ◽  
Tspo Expression ◽  
Frataxin Gene

Abstract Friedreich ataxia (FA) is caused by GAA repeat expansions in the first intron of FXN, the gene encoding frataxin, which results in decreased gene expression. Thanks to the high degree of frataxin conservation, the Drosophila melanogaster fruitfly appears as an adequate animal model to study this disease and to evaluate therapeutic interventions. Here, we generated a Drosophila model of FA with CRISPR/Cas9 insertion of approximately 200 GAA in the intron of the fly frataxin gene fh. These flies exhibit a developmental delay and lethality associated with decreased frataxin expression. We were able to bypass preadult lethality using genetic tools to overexpress frataxin only during the developmental period. These frataxin-deficient adults are short-lived and present strong locomotor defects. RNA-Seq analysis identified deregulation of genes involved in amino-acid metabolism and transcriptomic signatures of oxidative stress. In particular, we observed a progressive increase of Tspo expression, fully rescued by adult frataxin expression. Thus, Tspo expression constitutes a molecular marker of the disease progression in our fly model and might be of interest in other animal models or in patients. Finally, in a candidate drug screening, we observed that N-acetyl cysteine improved the survival, locomotor function, resistance to oxidative stress and aconitase activity of frataxin-deficient flies. Therefore, our model provides the opportunity to elucidate in vivo, the protective mechanisms of this molecule of therapeutic potential. This study also highlights the strength of the CRISPR/Cas9 technology to introduce human mutations in endogenous orthologous genes, leading to Drosophila models of human diseases with improved physiological relevance.

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