4,096 results match your criteria: "Friedreich Ataxia"
Pediatr Pulmonol
December 2024
The Cystic Fibrosis Center, Department of Pulmonary, Critical Care and Sleep Medicine, Lenox Hill Hospital, Northwell Health, New York, New York, USA.
Background: Newborn screening (NBS) for cystic fibrosis (CF) was universally implemented in the United States in 2010 to improve disease outcomes. Despite universal screening, disparities in outcomes currently exist between people with CF (PwCF) with Black/African, Asian, Indigenous, and Latino/Hispanic ancestry in comparison to PwCF of European ancestry. This is in part because CFTR panels used for newborn screening are often based on variants common in European ancestries leading to higher rates of false negatives for PwCF from minoritized racial and ethnic groups.
View Article and Find Full Text PDFCerebellum
December 2024
Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz" Campinas, Campinas, SP, 13083-887, Brazil.
Friedreich's Ataxia (FRDA) is the most common autosomal recessive ataxia worldwide and is caused by biallelic unstable intronic GAA expansions at FXN. With its limited therapy and the recent approval of the first disease-modifying agent for FRDA, the search for biological markers is urgently needed to assist and ease the development of therapies. MiRNAs have emerged as promising biomarkers in various medical fields such as oncology, cardiology, epilepsy and neurology as well.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, 00189 Rome, Italy.
For years, the treatment of many cardiomyopathies has been solely focused on symptom management. However, cardiomyopathies have a genetic substrate, and directing therapy towards the pathophysiology rather than the epiphenomenon of the disease may be a winning strategy. Gene therapy involves the insertion of genes or the modification of existing ones and their regulatory elements through strategies like gene replacement and gene editing.
View Article and Find Full Text PDFJ Cell Sci
December 2024
Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Friedreich's ataxia (FRDA) is a neurodegenerative disorder characterized by severe neurological signs, affecting the peripheral and central nervous system, caused by reduced frataxin protein (FXN) levels. While several studies highlight cellular dysfunctions in neurons, there is limited information on the effects of FXN depletion in astrocytes and on the potential non-cell autonomous mechanisms affecting neurons in FRDA. In this study, we generated a model of FRDA cerebellar astrocytes to unveil phenotypic alterations that might contribute to cerebellar atrophy.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Biology, Tufts University, Medford, MA, 02155, USA.
Trinucleotide repeats, including Friedreich's ataxia (GAA) repeats, become pathogenic upon expansions during DNA replication and repair. Here, we show that deficiency of the essential replisome component Mcm10 dramatically elevates (GAA) repeat instability in a budding yeast model by loss of proper CMG helicase interaction. Supporting this conclusion, live-cell microscopy experiments reveal increased replication fork stalling at the repeat in mcm10-1 cells.
View Article and Find Full Text PDFNeurology
December 2024
Division Translational Genomics of Neurodegenerative Diseases (L.B., A.T., D.M., M.S.), Hertie-Institute for Clinical Brain Research and Center for Neurology, and German Center for Neurodegenerative Diseases (DZNE) (L.B., A.T., D.M., K.D.-J., M.S., R.S.), University of Tübingen; Section Computational Sensomotorics (J.S., W.I.), Hertie Institute for Clinical Brain Research; Centre for Integrative Neuroscience (CIN) (J.S., W.I.); Department of Neurodegenerative Diseases (C.K.), Hertie-Institute for Clinical Brain Research and Center for Neurology, University of Tübingen; Center for Neurology and Hertie Institute for Clinical Brain Research (K.D.-J., R.S.), University Hospital Tübingen, Germany; Molecular Medicine (I.R., S.S.), IRCCS Fondazione Stella Maris, Pisa, Italy; Koç University (N.A.B.), Translational Medicine Research Center, KUTTAM-NDAL, Istanbul, Turkey; Sorbonne Université (G.C.), Paris Brain Institute, INSERM, CNRS, APHP, France; Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (D.T.), University Hospital Essen, University of Duisburg-Essen, Germany; Groupe de recherche interdisciplinaire sur les maladies neuromusculaires (GRIMN) (C.G.), Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-St-Jean; Centre de recherche du Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-St-Jean (C.G.); Faculté de médecine et des sciences de la santé (C.G.), Université de Sherbrooke, Québec, Canada; Department of Neurology (B.P.C.v.d.W.), Radboud University Medical Center, Nijmegen, the Netherlands; and Division of Neurodegenerative Diseases (R.S.), Department of Neurology, Heidelberg University Hospital, Germany.
Proc Natl Acad Sci U S A
December 2024
Department of Biology, Tufts University, Medford, MA 02155.
Am J Ophthalmol Case Rep
December 2024
Brain and Eye Pain Imaging Lab, Pain and Affective Neuroscience Center, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital/Harvard Medical School, 300 Longwood Avenue., Boston, MA, 02115, USA.
Purpose: Friedreich ataxia (FDRA) is a debilitating neurodegenerative disease that can have ophthalmological manifestations including visual dysfunction, nystagmus, and optic atrophy. However, severe photophobia has not been reported nor evaluated with functional magnetic resonance imaging (fMRI).
Methods: A 64-year-old white female with a 37-year history of FDRA presented to the eye clinic with worsening photophobia of 3 years.
Sci Rep
November 2024
Center of Hereditary Ataxias, Department of Neurology, 2nd Faculty of Medicine and Motol University Hospital, Charles University, Prague, Czech Republic.
Neuropsychiatric symptoms (NPS) are common in hereditary ataxias as a part of the cerebellar cognitive affective syndrome. In Friedreich ataxia (FRDA), one of the most common hereditary ataxias, depressive symptoms were previously reported, but little is known about other NPS. We aimed to study the presence and severity of a broad range of NPS in individuals with FRDA and assess the relationship between the NPS and the disease severity, cognition, and quality of life and to examine the concordance between the NPS reported by the patients and by their informants.
View Article and Find Full Text PDFNeuromuscul Disord
November 2024
Department of Epidemiology, College of Public Health, University of Iowa, S416 CPHB, 145 N Riverside Dr, Iowa City, Iowa 52242, United States. Electronic address:
Neurol Genet
December 2024
From the Department of Neurology (B.J.G., J.S.N., M.N.), O'Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas; Department of Neurology and Neurosurgery (D.P., B.B.), Montreal Neurological Hospital and Institute, McGill University, Montreal, Quebec, Canada; Department of Neuromuscular Diseases (D.P.), UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, University College London, United Kingdom; Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics (M.C.D., S.Z.), University of Miami Miller School of Medicine, FL; Department of Human Genetics (B.B.), McGill University, Montreal, Quebec, Canada; Laboratory of Genome Integrity (G.M.-R., A.N.), National Cancer Institute, NIH; Laboratory of Cell and Molecular Biology (K.U.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; and Department of Pediatrics and Neurology (C.C.P., D.R.L.), The Children's Hospital of Philadelphia, PA.
Mov Disord
November 2024
O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Int J Mol Sci
October 2024
Division of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Development (ENEA), 00123 Rome, Italy.
Friedreich ataxia (FRDA) is the most common inherited ataxia, primarily impacting the nervous system and the heart. It is characterized by GAA repeat expansion in the FXN gene, leading to reduced mitochondrial frataxin levels. Previously, we described a family displaying two expanded GAA alleles, not only in the proband affected by late-onset FRDA but also in the younger asymptomatic sister.
View Article and Find Full Text PDFInt J Equity Health
November 2024
School of Health Sciences, Swinburne University of Technology, Melbourne, Australia.
Friedreich Ataxia (FA) is an incurable neurodegenerative disease with systemic consequences affecting vital organs including those of the central and peripheral nervous systems. This article will use FA as an example to explore some of the practical and ethical issues emerging in precision medicine for rare diseases. It will first describe the existing management strategies available for FA patients, before considering the potential impact of gene therapy trials on the prevention and treatment of disease symptoms.
View Article and Find Full Text PDFNeurol Genet
December 2024
From the Department of Brain and Behavioural Sciences (P.M., A.P., C.T., M.A.), University of Pavia; IRCCS Mondino Foundation (E.V., R.Z., I.P., S.G., S.R.A., C.T., E.M.V., M.A.), Pavia, Italy; Department of Neurology and Neurosurgery (M.-J.D.), Montreal Neurological Hospital and Institute, McGill University, Quebec, Canada; Advanced Imaging Center and Artificial Intelligence (S.N., A.P.), Department of Neuroradiology, IRCCS Mondino Foundation; and Department of Molecular Medicine (E.M.V.), University of Pavia, Italy.
Objectives: To report a novel imaging finding of bilateral dentate nuclei hyperintensities in a case of childhood-onset GAA--related ataxia (spinocerebellar ataxia 27B, SCA27B) and response to 4-aminopyridine (4-AP).
Methods: A 53-year-old woman with unsolved progressive cerebellar ataxia of childhood onset underwent clinical and imaging assessment and extensive genetic investigation.
Results: After excluding Friedreich ataxia, most common spinocerebellar ataxia-related expansions, and pathogenic variants in ataxia-related genes through exome sequencing, targeted long-range PCR and repeat-primed PCR analysis revealed a heterozygous pathogenic (GAA) expansion in Brain MRI showed bilateral dentate nuclei hyperintensities and peridentate white matter degeneration, a feature never reported before in SCA27B.
Eur J Hum Genet
November 2024
Service de Médecine Génomique des Maladies Rares, Hôpital Necker - Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
Friedreich's Ataxia (FRDA) is the most common hereditary ataxia and is mainly caused by biallelic GAA repeat expansion in the FXN gene. Rare patients carrying FXN point mutations or intragenic deletions are reported. We describe the first FRDA patient with a chromosome 9 segmental Uniparental isoDisomy (UPiD) unmasking a homozygous FXN expansion initially undetected by TP-PCR.
View Article and Find Full Text PDFCommun Med (Lond)
October 2024
BioSensics LLC, Newton, MA, USA.
Background: Friedreich ataxia (FRDA) results in progressive impairment in gait, upper extremity coordination, and speech. Currently, these symptoms are assessed through expert examination at clinical visits. Such in-clinic assessments are time-consuming, subjective, of limited sensitivity, and provide only a limited perspective of the daily disability of patients.
View Article and Find Full Text PDFFASEB J
October 2024
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York, USA.
Pathogenic variants in the type I ryanodine receptor (RYR1) result in a wide range of muscle disorders referred to as RYR1-related myopathies (RYR1-RM). We developed the first RYR1-RM mouse model resulting from co-inheritance of two different RYR1 missense alleles (Ryr1 mice). Ryr1 mice exhibit a severe, early onset myopathy characterized by decreased body/muscle mass, muscle weakness, hypotrophy, reduced RYR1 expression, and unexpectedly, incomplete postnatal lethality with a plateau survival of ~50% at 12 weeks of age.
View Article and Find Full Text PDFNPJ Genom Med
October 2024
Laboratory for Comprehensive Genomic Analysis, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Mov Disord
September 2024
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain.
Mov Disord
September 2024
Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Clin Genet
October 2024
Department of Pediatrics, Division of Pediatric Neurology, Erciyes University Faculty of Medicine, Kayseri, Türkiye.
Genomic repeat sequences are patterns of nucleic acids that exist in multiple copies throughout the genome. More than 60 Mendelian disorders are caused by the expansion or contraction of these repeats. Various specific methods for determining tandem repeat variations have been developed.
View Article and Find Full Text PDFNeurol Sci
December 2024
Univ Angers, Nantes Université, LPPL, SFR CONFLUENCES, UR4638, F-49000, Angers, France.
Background: The onset of the symptoms of subcortical NDs is due to a unique part of the brain which strengthens the idea of reciprocal influence of physical activity and cognitive training in improving clinical symptoms. Consequently, protocols combining the two stimulations are becoming increasingly popular in NDs. Our threefold aim was to (A) describe the different combinations of physical and cognitive training used to alleviate the motor and cognitive symptoms of patients with subcortical neurodegenerative disorders, (B) compare the effects of these different combinations (sequential, dual tasking, synergical) on symptoms, and (C) recommend approaches for further studies.
View Article and Find Full Text PDFClin Pharmacol Drug Dev
November 2024
Clario, Philadelphia, PA, USA.
Vatiquinone, a 15-lipoxygenase inhibitor, is in development for patients with Friedreich ataxia. The study determined the effect of vatiquinone on electrocardiogram parameters. This was a 2-part, single-center, randomized, double-blinded, and placebo-controlled study.
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