ArticleHuman mutation2020
A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders.
Article in Human mutation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Spinocerebellar ataxia 27B (SCA27B)-a systematic review and a case report of a Polish family.Journal of applied genetics · 2025Pooled it
- Diagnostic Yield of NGS Tests for Hereditary Ataxia: a Systematic Review.Cerebellum (London, England) · 2024Pooled it
- Frequency of ZFHX3-Mediated Spinocerebellar Ataxia 4 in a US Undiagnosed Ataxia Cohort.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Exclusion of CLIC5 as a Candidate Gene and Identification of NEFM as a Possible Novel Gene Correlated With Autosomal Recessive Pure Cerebellar Ataxia in a Highly Consanguineous Family.Molecular genetics & genomic medicine · 2026Article
- Genetic insights: proband- only exome sequencing in pediatric neurological disorders.Journal of community genetics · 2026Article
- Expanding the Early Childhood Manifestations ofNeurology. Genetics · 2026Article
- Novel homozygousTherapeutic advances in neurological disorders · 2026Article
- Identification of a novelFrontiers in genetics · 2026Article
- Whole exome sequencing in Japanese spinocerebellar ataxia identifies novel variants.Journal of human genetics · 2026Article
- Past, present, and future of genomic technologies in cerebellar ataxias.Journal of neurology · 2025Review
- High Genetic Diagnostic Yield for Patients with Rare Movement Disorders at a Single-Center Neurogenetics Clinic.Movement disorders clinical practice · 2025Article
- Autosomal Recessive Cerebellar Ataxias: Translating Genes to Therapies.Annals of neurology · 2025Review
- RFC1 regulates the expansion of neural progenitors in the developing zebrafish cerebellum.Nature communications · 2025Article
- The molecular landscape of hereditary ataxia: a single-center study.Human genetics · 2025Article
- A prospective trial comparing programmable targeted long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia.Genome research · 2025Article
- Diagnosis of hereditary ataxias: a real-world single center experience.Journal of neurology · 2025Article
- Diagnostic yield and limitations of whole-genome sequencing for hereditary cerebellar ataxia.Brain communications · 2025Article
- Roles of KCNA2 in Neurological Diseases: from Physiology to Pathology.Molecular neurobiology · 2024Review
- Valuable insights into hereditary spinocerebellar degeneration from clusters of homozygosity in Africa.European journal of human genetics : EJHG · 2024Article
- Genetic aspects of ataxias in a cohort of Turkish patients.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
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Authors and funding
26 authors.
Funding
Abstract
Genetic ataxias are associated with mutations in hundreds of genes with high phenotypic overlap complicating the clinical diagnosis. Whole-exome sequencing (WES) has increased the overall diagnostic rate considerably. However, the upper limit of this method remains ill-defined, hindering efforts to address the remaining diagnostic gap. To further assess the role of rare coding variation in ataxic disorders, we reanalyzed our previously published exome cohort of 76 predominantly adult and sporadic-onset patients, expanded the total number of cases to 260, and introduced analyses for copy number variation and repeat expansion in a representative subset. For new cases (n = 184), our resulting clinically relevant detection rate remained stable at 47% with 24% classified as pathogenic. Reanalysis of the previously sequenced 76 patients modestly improved the pathogenic rate by 7%. For the combined cohort (n = 260), the total observed clinical detection rate was 52% with 25% classified as pathogenic. Published studies of similar neurological phenotypes report comparable rates. This consistency across multiple cohorts suggests that, despite continued technical and analytical advancements, an approximately 50% diagnostic rate marks a relative ceiling for current WES-based methods and a more comprehensive genome-wide assessment is needed to identify the missing causative genetic etiologies for cerebellar ataxia and related neurodegenerative diseases.
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