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Víctor Volpini

Bio: Víctor Volpini is an academic researcher. The author has contributed to research in topics: Trinucleotide repeat expansion & Olivopontocerebellar atrophy. The author has an hindex of 1, co-authored 1 publications receiving 3 citations.

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Journal ArticleDOI
TL;DR: A Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon is described.
Abstract: The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow ocular saccades, nystagmus, ophthalmoplegia, dysarthria, dysphagia, cognitive deterioration, mild dementia, peripheral neuropathy. Infantile onset is a rare presentation that only has been reported in four instances in the literature. In the present work a boy aged 5 years 7 months was studied due to horizontal gaze-evoked nystagmus, without saccades, ataxic gait, dysarthria, dysphagia, dysmetria, generalized spasticity mainly pelvic, bilateral Babinsky. The mother aged 27 years-old presented progressive cerebellar ataxia, dysarthria, dysmetria, dysdiadochokinesis, limb ataxia and olivopontocerebellar atrophy. The molecular analysis was made by identifying the expansion repeats in tandem by long PCR to analyze the repeats in the ATXN2 gene. We found an extreme CAG expansion repeats of ~884 repeats in the child. We describe a Mexican child affected by SCA2 with an infantile onset, associated with a high number of CAG repeats previously no reported and anticipation phenomenon.

7 citations


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Journal ArticleDOI
TL;DR: The role of ATXN2 and its variants in association with SCA2 and several other neurological diseases has been discussed in this paper, including motor neuron disease, spinocerebellar ataxia 3 (SCA3), and familial amyloidosis polyneuropathy.
Abstract: Purpose of review To provide an update on the role of Ataxin-2 gene (ATXN2) in health and neurological diseases. Recent findings There is a growing complexity emerging on the role of ATXN2 and its variants in association with SCA2 and several other neurological diseases. Polymorphisms and intermediate cytosine adenine guanine alleles in ATXN2 establish this gene as a powerful modulator of neurological diseases including lethal neurodegenerative conditions such as motor neuron disease, spinocerebellar ataxia 3 (SCA3), and peripheral nerve disease such as familial amyloidosis polyneuropathy. This role is in fact far wider than the previously described for polymorphism in the prion protein (PRNP) gene. Positive data from antisense oligo therapy in a murine model of SCA2 suggest that similar approaches may be feasible in humans SCA2 patients. Summary ATXN2 is one of the few genes where a single gene causes several diseases and/or modifies several and disparate neurological disorders. Hence, understanding mutagenesis, genetic variants, and biological functions will help managing SCA2, and several human diseases connected with dysfunctional pathways in the brain, innate immunity, autophagy, cellular, lipid, and RNA metabolism.

11 citations

Journal ArticleDOI
TL;DR: The authors performed a bioinformatics review of published RNAseq polyglutamine expression data resulting from the presence of polyQ genes in search of neurodevelopmental expression patterns and comparison between diseases.
Abstract: Polyglutamine (PolyQ) diseases are neurodegenerative disorders caused by the CAG repeat expansion mutation in affected genes resulting in toxic proteins containing a long chain of glutamines. There are nine PolyQ diseases: Huntington's disease (HD), spinocerebellar ataxias (types 1, 2, 3, 6, 7, and 17), dentatorubral-pallidoluysian atrophy (DRPLA), and spinal bulbar muscular atrophy (SBMA). In general, longer CAG expansions and longer glutamine tracts lead to earlier disease presentations in PolyQ patients. Rarely, cases of extremely long expansions are identified for PolyQ diseases, and they consistently lead to juvenile or sometimes very severe infantile-onset polyQ syndromes. In apparent contrast to the very long CAG tracts, shorter CAGs and PolyQs in proteins seems to be the evolutionary factor enhancing human cognition. Therefore, polyQ tracts in proteins can be modifiers of brain development and disease drivers, which contribute neurodevelopmental phenotypes in juvenile- and adult-onset PolyQ diseases. Therefore we performed a bioinformatics review of published RNAseq polyQ expression data resulting from the presence of polyQ genes in search of neurodevelopmental expression patterns and comparison between diseases. The expression data were collected from cell types reflecting stages of development such as iPSC, neuronal stem cell, neurons, but also the adult patients and models for PolyQ disease. In addition, we extended our bioinformatic transcriptomic analysis by proteomics data. We identified a group of 13 commonly downregulated genes and proteins in HD mouse models. Our comparative bioinformatic review highlighted several (neuro)developmental pathways and genes identified within PolyQ diseases and mouse models responsible for neural growth, synaptogenesis, and synaptic plasticity.

6 citations

Journal ArticleDOI
TL;DR: This work overviews the role of non-polyQ regions that control the pathogenicity of the expanded polyQ repeat and provides a survey of protein-protein interactions and posttranslational modifications that regulate polyQ toxicity.
Abstract: The presence and aggregation of misfolded proteins has deleterious effects in the nervous system. Among the various diseases caused by misfolded proteins is the family of the polyglutamine (polyQ) disorders. This family comprises nine members, all stemming from the same mutation—the abnormal elongation of a polyQ repeat in nine different proteins—which causes protein misfolding and aggregation, cellular dysfunction and disease. While it is the same type of mutation that causes them, each disease is distinct: it is influenced by regions and domains that surround the polyQ repeat; by proteins with which they interact; and by posttranslational modifications they receive. Here, we overview the role of non-polyQ regions that control the pathogenicity of the expanded polyQ repeat. We begin by introducing each polyQ disease, the genes affected, and the symptoms experienced by patients. Subsequently, we provide a survey of protein-protein interactions and posttranslational modifications that regulate polyQ toxicity. We conclude by discussing shared processes and pathways that bring some of the polyQ diseases together and may serve as common therapeutic entry points for this family of incurable disorders.

4 citations

Posted ContentDOI
17 Oct 2022
TL;DR: In this article , a TR-FRET-based immunoassay was used to measure polyQ-expanded ataxin-2 in human biomaterials and validated measurements in human cell lines including primary skin fibroblasts, induced pluripotent stem cells (iPSCs) and iPSC-derived cortical neurons.
Abstract: Abstract Background Spinocerebellar Ataxia Type 2 (SCA2) belongs to a group of neurodegenerative diseases, inherited as an autosomal dominant trait. SCA2 is a trinucleotide repeat disease with a CAG repeat expansion in exon 1 of the ATXN2 gene resulting in an ataxin-2 protein with an expanded polyglutamine (polyQ)-stretch. The disease is late manifesting leading to premature death. Today, therapeutic interventions to cure the disease or even to decelerate disease progression are not available yet. Furthermore, primary readout parameter for disease progression and therapeutic intervention studies are limited. Thus, there is an urgent need for quantifiable molecular biomarkers such as ataxin-2 becoming even more important due to numerous potential protein reducing therapeutic intervention strategies. Objective Aim of this study was to establish a sensitive technique to measure the amount of polyQ-expanded ataxin-2 in human biofluids to evaluate ataxin-2 protein levels as prognostic and/ -or therapeutic biomarker in SCA2. Methods Time-Resolved Fluorescence Energy Transfer (TR-FRET) was used to establish a polyQ-expanded ataxin-2-specific immunoassay. Two different ataxin-2 antibodies and two different polyQ-binding antibodies were validated in three different concentrations and tested in cellular and animal tissue as well as in human cell lines, comparing different buffer conditions as well as total protein concentrations to evaluate the best assay conditions. Results We established a TR-FRET-based immunoassay for polyQ-expanded ataxin-2 and validated measurements in human cell lines including primary skin fibroblasts, induced pluripotent stem cells (iPSCs) and iPSC-derived cortical neurons. Additionally, our immunoassay was sensitive enough to monitor small ataxin-2 expression changes by siRNA or starvation treatment. Conclusion We successfully established the first sensitive ataxin-2 immunoassay to measure specifically polyQ-expanded ataxin-2 in human biomaterials.
Journal ArticleDOI
TL;DR: In this paper , the amount of soluble polyQ-expanded ataxin-2 in human biofluids was measured using time-resolved fluorescence energy transfer (TR-FRET) and validated measurements in human cell lines including iPSC-derived cortical neurons.
Abstract: Abstract Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease, which belongs to the trinucleotide repeat disease group with a CAG repeat expansion in exon 1 of the ATXN2 gene resulting in an ataxin-2 protein with an expanded polyglutamine (polyQ)-stretch. The disease is late manifesting leading to early death. Today, therapeutic interventions to cure the disease or even to decelerate disease progression are not available yet. Furthermore, primary readout parameter for disease progression and therapeutic intervention studies are limited. Thus, there is an urgent need for quantifiable molecular biomarkers such as ataxin-2 becoming even more important due to numerous potential protein-lowering therapeutic intervention strategies. The aim of this study was to establish a sensitive technique to measure the amount of soluble polyQ-expanded ataxin-2 in human biofluids to evaluate ataxin-2 protein levels as prognostic and/or therapeutic biomarker in SCA2. Time-resolved fluorescence energy transfer (TR-FRET) was used to establish a polyQ-expanded ataxin-2-specific immunoassay. Two different ataxin-2 antibodies and two different polyQ-binding antibodies were validated in three different concentrations and tested in cellular and animal tissue as well as in human cell lines, comparing different buffer conditions to evaluate the best assay conditions. We established a TR-FRET-based immunoassay for soluble polyQ-expanded ataxin-2 and validated measurements in human cell lines including iPSC-derived cortical neurons. Additionally, our immunoassay was sensitive enough to monitor small ataxin-2 expression changes by siRNA or starvation treatment. We successfully established the first sensitive ataxin-2 immunoassay to measure specifically soluble polyQ-expanded ataxin-2 in human biomaterials.