Inherited Cerebellar Ataxias: 5-Year Experience of the Irish National Ataxia Clinic

Bogdanova-Mihaylova, Petya; Hebert, Josephine; Moran, Sharon; Murphy, Michael; Ward, Deirdre; Walsh, Richard A.; Murphy, S. M.

doi:10.1007/s12311-020-01180-0

Cited by 21 publications

(17 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The diagnostic rate (33.2%) obtained in our study was nearly twofold the average weighted value described in the TRP-based studies of HA (19.4%) reported in the literature, and comparable to the value reported in those using ES as a first-tier approach (34.6%). Considering the high coverage reached with multigene panels, and the easier and faster analysis of their results compared with the more commonly used ES method (where low, not always uniform coverage might result in gaps), it can be argued-as others have done [93]-that multigene panels are still worth using for quick screening of large cohorts. Our results indicate that the large multigene panel we designed would have intercepted 97.5% (235/241) of the diagnosed cases in published TRP series (excluding those with mtDNA mutations) and most of those solved by ES (92.2%; 376/408) (Table S8).…”

Section: Discussionmentioning

confidence: 99%

NGS in Hereditary Ataxia: When Rare Becomes Frequent

Galatolo

Michele

Silvestri

et al. 2021

IJMS

View full text Add to dashboard Cite

The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia-dominated phenotypes. Massive gene analysis in next-generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis. STUB1, PRKCG, and SPG7 were the most common causative genes. A comparison with published literature data showed that our panel would have identified 97% of the positive cases reported in previous TRP-based studies and 92% of those diagnosed by ES. Proper use of multigene panels, when combined with detailed phenotypic data, seems to be even more efficient than ES in clinical practice.

show abstract

Section: Discussionmentioning

confidence: 99%

NGS in Hereditary Ataxia: When Rare Becomes Frequent

Galatolo

Michele

Silvestri

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…More information on the utility of NGS in early-onset cerebellar ataxias (EOCAs) comes from studies on larger series of adults, whose symptoms started appearing before the age of 40. Overall, they showed a diagnostic yield of NGS ranging from 21% to over 50%, with higher percentages of molecular diagnoses in patients with a positive family history compatible with Mendelian inheritance [20,[32][33][34][35][36][37][38][39]. The results of NGS studies outlined the most common etiologies of EOCAs in different populations.…”

Section: Utility Of Next-generation Sequencing In Childhood-onset Cerebellar Ataxiasmentioning

confidence: 95%

“…Studies show that AD has a significant polygenic component, which may be used in calculating genetic risk of developing the disease. The sum of risk alleles carried by an individual, where each single nucleotide polymorphism (SNP) is weighted by the effect [20,21,24,[32][33][34][35][36] size from the prior GWAS, is called a polygenic risk score (PRS) and may have a predictive value for multiple common diseases. Promising results that point to potential clinical utility of PRS in the future have been published for AD and epilepsy [63,64].…”

Section: Cerebellar Ataxias-beyond Monogenic Diseasesmentioning

confidence: 99%

“…Klockgether and Giordano et al [ 1 , 48 ] estimated that testing for common tandem repeat expansions, followed by ataxia-specific NGS panel, may result in genetic diagnosis in about 20% of apparently SAOAs. Apart from detecting ultrarare monogenic causes, NGS studies outlined several genes commonly implicated in adult-onset CAs, such as SYNE1 , SPG7 , and ANO10 [ 34 , 36 , 44 ]. Importantly, a significant number of patients classified as CAs were found to carry pathogenic variants traditionally associated with hereditary spastic paraplegias (HSPs).…”

Section: Utility Of Next-generation Sequencing In Adult-onset Cerebellar Ataxiasmentioning

confidence: 99%

See 1 more Smart Citation

Milestones in genetics of cerebellar ataxias

Krygier

Mazurkiewicz-Bełdzińska

2021

Neurogenetics

View full text Add to dashboard Cite

Cerebellar ataxias (CAs) comprise a group of rare, neurological disorders characterized by extensive phenotypic and genetic heterogeneity. The core clinical feature is the cerebellar syndrome, which is often accompanied by other neurological or non-neurological signs. In the last 30 years, our understanding of the CA etiology has increased significantly, and numerous ataxia-associated genes have been discovered. Conventional variants or tandem repeat expansions, localized in the coding or non-coding DNA sequences, lead to hereditary ataxia, which can display different patterns of inheritance. Advances in molecular techniques have enabled a rapid and cost-effective detection of causative variants in a significant number of CA patients. However, despite performing extensive investigations, a definite diagnosis is still unknown in the majority of affected individuals. In this review, we discuss the major advances in the genetics of CAs over the last 30 years, focusing on the impact of next-generation sequencing on the genetic landscape of childhood- and adult-onset CAs. Additionally, we outline possible directions for further genetic research in hereditary and sporadic CAs in the era of increasing application of whole-genome sequencing and genome-wide association studies in various neurological disorders.

show abstract

“…Provision of disease monitoring and clinical care can therefore be challenging. Friedreich's ataxia (FRDA), the most common inherited ataxia [1], has an estimated prevalence of 1/20,000-1/50,000 amongst Caucasians and Ireland has one of the highest estimated prevalence rates in Europe at 1/23,000 [2]. Despite this, no studies to date have assessed healthcare costs or resource utilisation of inherited ataxia in Ireland.…”

Section: Introductionmentioning

confidence: 99%

The Cost of Living with Inherited Ataxia in Ireland

et al. 2021

Self Cite

View full text Add to dashboard Cite

Inherited ataxias are a heterogenous group of neurodegenerative disorders characterised by progressive impairment of balance and coordination, typically leading to permanent and progressive disability. Diagnosis and management of these disorders incurs a range of direct and indirect financial costs. The aim of this study was to collect individual ataxia-related healthcare resources in a large cohort of individuals with different subtypes of inherited ataxia and calculate the associated cost of illness in the Republic of Ireland. One hundred twenty-nine respondents completed a cross-sectional study on healthcare resource utilisation for progressive ataxia in Ireland. Costs were calculated using a prevalence-based approach and bottom-up methodology. The COI for inherited ataxia in 2016 was €59,993 per person per year. Results were similar between participants with Friedreich’s ataxia (FRDA, n = 56), non-FRDA (n = 18) and those with undetermined ataxia (n = 55). Indirect costs, based on productivity losses by participants or caregivers, accounted for 52% of the cost of illness. Inherited ataxia is associated with significant health and social care costs. Further funding for inherited ataxia to ease the financial burden on patients, caregivers and healthcare system and improve standards of care compliance is warranted.

show abstract

Inherited Cerebellar Ataxias: 5-Year Experience of the Irish National Ataxia Clinic

Cited by 21 publications

References 35 publications

NGS in Hereditary Ataxia: When Rare Becomes Frequent

NGS in Hereditary Ataxia: When Rare Becomes Frequent

Milestones in genetics of cerebellar ataxias

The Cost of Living with Inherited Ataxia in Ireland

Contact Info

Product

Resources

About