Next-generation sequencing and bioinformatics in rare movement disorders

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(2), P. 114 - 126

Published: Jan. 3, 2024

Language: Английский

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Hereditary Ataxias: From Bench to Clinic, Where Do We Stand?

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 319 - 319

Published: Feb. 9, 2024

Cerebellar ataxias are a wide heterogeneous group of movement disorders. Within this broad umbrella diseases, there both genetics and sporadic forms. The clinical presentation these conditions can exhibit diverse range symptoms across different age groups, spanning from pure cerebellar manifestations to sensory ataxia multisystemic diseases. Over the last few decades, advancements in our understanding molecular pathophysiology related dominant recessive have propelled field forward, paving way for innovative therapeutic strategies aimed at preventing arresting progression Nevertheless, rarity certain forms continues pose challenges, leading limited insights into etiology disease identification target pathways. Additionally, lack suitable models hampers efforts comprehensively understand foundations disease’s test novel interventions. In following review, we describe epidemiology, symptomatology, pathological hereditary ataxia, including prevalent less common Furthermore, illustrate pathways approaches currently undergoing investigation pre-clinical studies trials. Finally, address existing anticipated challenges within field, encompassing basic research endeavors.

Language: Английский

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Big data and transformative bioinformatics in genomic diagnostics and beyond

Parkinsonism & Related Disorders, Journal Year: 2025, Volume and Issue: unknown, P. 107311 - 107311

Published: Feb. 1, 2025

The current era of high-throughput analysis-driven research offers invaluable insights into disease etiologies, accurate diagnostics, pathogenesis, and personalized therapy. In the field movement disorders, investigators are facing an increasing growth in volume produced patient-derived datasets, providing substantial opportunities for precision medicine approaches based on extensive information accessibility advanced annotation practices. Integrating data from multiple sources, including phenomics, genomics, multi-omics, is crucial comprehensively understanding different types disorders. Here, we explore formats analytics big generated patients with strategies to meaningfully share optimized patient benefit. We review computational methods that essential accelerate process evaluating amounts specialized collected. Based concrete examples, highlight how bioinformatic facilitate translation multidimensional biological clinically relevant knowledge. Moreover, outline feasibility computer-aided therapeutic target evaluation, discuss importance expanding focus understudied phenotypes such as dystonia.

Language: Английский

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Hereditary Ataxias in Argentina

The Cerebellum, Journal Year: 2025, Volume and Issue: 24(3)

Published: April 8, 2025

Language: Английский

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The molecular landscape of hereditary ataxia: a single-center study

Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Language: Английский

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MRI‐ARSACS: An Imaging Index for Autosomal Recessive Spastic Ataxia of Charlevoix‐Saguenay (ARSACS) Identification Based on the Multicenter PROSPAX Study

Movement Disorders, Journal Year: 2024, Volume and Issue: 39(8), P. 1343 - 1351

Published: June 7, 2024

Abstract Background Autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) and hereditary paraplegia type 7 (SPG7) represent the most common genotypes (SPAX). To date, their magnetic resonance imaging (MRI) features have only been described qualitatively, a pure neuroradiological differential diagnosis between these two conditions is difficult to achieve. Objectives test performance MRI measures discriminate ARSACS SPG7 (as an index SPAX disease). Methods In this prospective multicenter study, 3D‐T1‐weighted images 59 (35.4 ± 10.3 years, M/F = 33/26) 78 (54.8 51/27) patients PROSPAX Consortium were analyzed, together with 30 controls (45.9 16.9 15/15). Different linear surface evaluated. A receiver operating characteristic analysis was performed, calculating area under curve (AUC) corresponding diagnostic accuracy parameters. Results The pons proved be metric increased exclusively in ( P 0.02). Other different reduced compared (all ≤ 0.005). cut‐off value equal 1.67 pons‐to‐superior vermis ratio highest AUC (0.98, 93%, sensitivity 97%) discriminating SPG7. Conclusions Evaluation can from other patients, as exemplified here by Hence, we hereby propose Magnetic Resonance Index for Assessment Recognition harboring SACS mutations (MRI‐ARSACS), novel tool able identify useful undergoing MRI. © 2024 International Parkinson Movement Disorder Society.

Language: Английский

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The genetic basis of early-onset hereditary ataxia in Iran: results of a national registry of a heterogeneous population

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: April 3, 2024

Abstract Background To investigate the genetics of early-onset progressive cerebellar ataxia in Iran, we conducted a study at Children’s Medical Center (CMC), primary referral center for pediatric disorders country, over three-year period from 2019 to 2022. In this report, provide initial findings national registry. Methods We selected all patients with an autosomal recessive mode inheritance assess their phenotype, paraclinical tests, and genotypes. The clinical data encompassed features, Scale Assessment Rating Ataxia (SARA) scores, Magnetic Resonance Imaging (MRI) results, Electrodiagnostic exams (EDX), biomarker features. Our genetic investigations included single-gene testing, Whole Exome Sequencing (WES), Genome (WGS). Results enrolled 162 various geographic regions our country. Among subpopulations, identified known novel pathogenic variants 42 genes 97 families. overall diagnostic rate was 59.9%. Notably, observed PLA2G6 , ATM SACS SCA 19, 14, 12, 10 families, respectively. Remarkably, more than 59% cases were attributed these genes. Conclusions being crossroad Middle East, exhibits highly diverse etiology hereditary ataxia. light heterogeneity, development preventive strategies targeted molecular therapeutics becomes crucial. A guideline diagnosis management conditions could significantly aid advancing healthcare approaches improving patient outcomes.

Language: Английский

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CHARON: An Imaging-Based Diagnostic Algorithm to Navigate Through the Sea of Hereditary Degenerative Ataxias

The Cerebellum, Journal Year: 2024, Volume and Issue: 23(5), P. 2122 - 2129

Published: March 4, 2024

Abstract The complexity in diagnosing hereditary degenerative ataxias lies not only their rarity, but also the variety of different genetic conditions that can determine sometimes similar and overlapping clinical findings. In this light, Magnetic Resonance Imaging (MRI) plays a key role evaluation these conditions, being fundamental diagnostic tool needed to exclude other causes determining observed phenotype, proper guide an adequate testing. Here, we propose MRI-based algorithm named CHARON (Characterization Hereditary Ataxias Relying On Neuroimaging), help disentangling among numerous, apparently very similar, ataxias. Being conceived from neuroradiological standpoint, it is based primarily on accurate MRI findings, with first most important pattern cerebellar atrophy. Along presence, or absence, additional signal changes and/or supratentorial involvement, allows for identification small groups sharing imaging features. integration demographic, laboratory data allow then typical, some cases pathognomonic, phenotypes

Language: Английский

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Molecular diagnostic approach to rare neurological diseases from a clinician viewpoint

Genomics & Informatics, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 10, 2024

Advancements in sequencing technology have significantly enhanced diagnostic capabilities for rare neurological diseases. This progress molecular diagnostics can greatly impact clinical management and facilitate the development of personalized treatments patients with Neurologists expertise should raise awareness, as phenotyping remains crucial making a diagnosis, even genomics era. They prioritize different types genomic tests, considering both benefits limitations inherent to each test. Notably, long-read is being utilized cases suspected involve repeat expansion disorders or complex structural variants. Repeat are highly prevalent diseases, particularly within ataxia group. Significant efforts, including periodic reanalysis, data sharing, integration multi-omics studies, be directed toward that remain undiagnosed after standard next-generation sequencing.

Language: Английский

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CRPD frontiers in movement disorders Therapeutics: From evidence to treatment and applications

Clinical Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 10, P. 100255 - 100255

Published: Jan. 1, 2024

The genetic ataxias have no cures and proven ways to delay progression (no disease-modifying therapies). acquired may treatments that address the underlying cause slow or stop progression, but will not reverse damage already sustained. idiopathic (of unknown cause) also therapies. However, for all patients with ataxia of any cause, there is always something can be done improve quality life-treat associated symptoms, provide information resources, counsel patient family, help insurance disability concerns, available listen answer many questions they have.

Language: Английский

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