Spinocerebellar Ataxia Tethering PCR: A Rapid Genetic Test for the Diagnosis of Spinocerebellar Ataxia Types 1, 2, 3, 6, and 7 by PCR and Capillary Electrophoresis

Publication date: May 2018Source: The Journal of Molecular Diagnostics, Volume 20, Issue 3Author(s): Claudia Cagnoli, Alessandro Brussino, Cecilia Mancini, Marina Ferrone, Laura Orsi, Paola Salmin, Patrizia Pappi, Elisa Giorgio, Elisa Pozzi, Simona Cavalieri, Eleonora Di Gregorio, Marta Ferrero, Alessandro Filla, Giuseppe De Michele, Cinzia Gellera, Caterina Mariotti, Suran Nethisinghe, Paola Giunti, Giovanni Stevanin, Alfredo BruscoSpinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7, associated with a (CAG)n repeat expansion in coding sequences, are the most prevalent autosomal dominant ataxias worldwide (approximately 60% of the cases). In addition, the phenotype of SCA2 expansions has been now extended to Parkinson disease and amyotrophic lateral sclerosis. Their diagnosis is currently based on a PCR to identify small expanded alleles, followed by a second-level test whenever a false normal homozygous or a CAT interruption in SCA1 needs to be verified. Next-generation sequencing still does not allow efficient detection of these repeats. Here, we show the efficacy of a novel, rapid, and cost-effective method to identify and size pathogenic expansions in SCA1, 2, 3, 6, and 7 and recognize large alleles or interruptions without a second-level test. Twenty-five healthy controls and 33 expansion carriers were analyzed: alleles migrated consistently in different PCRs and capillary runs, and homozygous individuals were always distinguishable from heterozygous carriers of both co...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research

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Abstract Neurodegenerative diseases (NDDs) are incapacitating disorders that result in progressive motor and cognitive impairment. These disease include Alzheimer's disease the most common cause of dementia, frontotemporal dementia, amyotrophic lateral sclerosis, dementia with Lewy bodies, Parkinson's, Huntington's, Friedreich's ataxia, and prion disease. Dementia causing NDDs impose a high social and economic burden on communities around the world. Rapid growth in knowledge regarding the pathogenic mechanisms and disease-associated biomarkers of these diseases in the past few decades have accelerated the developm...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research
Publication date: May 2018 Source:Neurochemistry International, Volume 115 Author(s): Zhihui Zhu, Georg Reiser Small heat shock proteins (sHsps) are a group of proteins with molecular mass between 12 and 43 kDa. Currently, 11 members of this family have been classified, namely HspB1 to HspB11. HspB1, HspB2, HspB5, HspB6, HspB7, and HspB8, which are expressed in brain have been observed to be related to the pathology of neurodegenerative diseases, including Parkinson's, Alzheimer's, Alexander's disease, multiple sclerosis, and human immunodeficiency virus-associated dementia. Specifically, sHsps interact with misfolding ...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
Publication date: Available online 17 February 2018 Source:The Journal of Molecular Diagnostics Author(s): Claudia Cagnoli, Alessandro Brussino, Cecilia Mancini, Marina Ferrone, Laura Orsi, Paola Salmin, Patrizia Pappi, Elisa Giorgio, Elisa Pozzi, Simona Cavalieri, Eleonora Di Gregorio, Marta Ferrero, Alessandro Filla, Giuseppe De Michele, Cinzia Gellera, Caterina Mariotti, Suran Nethisinghe, Paola Giunti, Giovanni Stevanin, Alfredo Brusco Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7, associated with a (CAG)n repeat expansion in coding sequences, are the most prevalent autosomal dominant ataxias worldwide (approxi...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research
This article is protected by copyright. All rights reserved. PMID: 29513402 [PubMed - as supplied by publisher]
Source: Immunology - Category: Allergy & Immunology Authors: Tags: Immunology Source Type: research
Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7, associated with a (CAG)n repeat expansion in coding sequences, are the most prevalent autosomal dominant ataxias worldwide (approximately 60% of the cases). In addition, the phenotype of SCA2 expansions has been now extended to Parkinson disease and amyotrophic lateral sclerosis. Their diagnosis is currently based on a PCR to identify small expanded alleles, followed by a second-level test whenever a false normal homozygous or a CAT interruption in SCA1 needs to be verified.
Source: Journal of Molecular Diagnostics - Category: Pathology Authors: Tags: Regular article Source Type: research
AbstractDeregulated neurotrophin is an etiological factor in the pathology of neurodegenerative diseases (ND) that are clinically different entities but characterised by similar limb dysfunction. Earlier validation of peripheral biomarkers can provide significant translational benefit to ND patients. We analysed brain-derived neurotrophic factor (BDNF) –tropomyosin possessing tyrosine-related kinase (Trk B) and its key downstream proteins which are implicated in ND such as Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and ataxia. Blood from ND patients with PD, ALS and Ataxia with movement dysfu...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
Authors: Liu J, Wang LN Abstract Neurodegenerative movement disorders mainly include Parkinson's disease, atypical parkinsonisms, Huntington disease, and hereditary ataxia. Riluzole is the only drug approved by the US Food and Drug Administration for amyotrophic lateral sclerosis. The neuroprotective effects of riluzole have been observed in experimental models of neurodegenerative movement disorders. In this paper, we aimed to systematically analyze the efficacy and safety of riluzole for patients with neurodegenerative movement disorder. We searched the electronic databases such as PubMed, EMBASE, CINAHL, Cochran...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research
AbstractThe clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping symptoms. It does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same disorder. The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. With the plethora of new genes being identified, genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia (SCA), hereditary spastic ...
Source: Translational Neurodegeneration - Category: Neurology Source Type: research
ConclusionsThe CAG‐expansion in ATXN2 likely caused the ataxia, whereas the dementia may be linked to both C9orf72 and ATXN2 repeat expansions. The pathological uninterrupted ATXN2 repeat may not have the same modifying effect as intermediate interrupted alleles. © 2016 International Parkinson and Movement Disorder Society.
Source: Movement Disorders - Category: Neurology Authors: Tags: Brief Report Source Type: research
Authors: Islam MT Abstract Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body's antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA. Oxidative stress has been considered to be linked to th...
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
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