ArticleNature communications2024
Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Clinical and Genetic Characteristics of SCA27B: A Global Systematic Review and Meta-Analysis.Cerebellum (London, England) · 2026Pooled it
- Spinocerebellar ataxia 27B (SCA27B)-a systematic review and a case report of a Polish family.Journal of applied genetics · 2025Pooled it
- Hereditary and Non-hereditary Cerebellar Ataxias in Latvia: Six Years of Experience at the National Reference Centre (ERN-RND Affiliated Partner).Cerebellum (London, England) · 2026Article
- Toward the clinical application of long-read sequencing in repeat-expansion disorders.Nature genetics · 2026Review
- GAA-FGF14 Ataxia Is a Frequently Overlooked Cause of Sporadic Adult-Onset Ataxia.Clinical genetics · 2026Article
- Optimized Cas9-Enriched Nanopore Sequencing and Analysis Workflow for Clinical Diagnosis of Repeat Expansion Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Frequency and phenotype of GAA-FGF14 disease in bilateral vestibulopathy syndromes: insights from repeat expansion carriers, including a case of co-occurrence with RFC1-related CANVAS.Journal of neurology · 2026Article
- Identification of FGF14 GAA Expansions in Polish Patients with Undiagnosed Cerebellar Ataxia - A Preliminary Study.Cerebellum (London, England) · 2026Article
- Long-read sequencing identifies FGF14 repeat expansions in Parkinson's disease.Brain : a journal of neurology · 2026Article
- Clinical, Genetic, and Imaging Characteristics of SCA27B: Insights from a Large Dutch Cohort.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Pathogenic CGG expansions in oculopharyngodistal myopathy exhibit distinct characteristics of each causative gene on the flanking sequences as well as methylation status.Genome medicine · 2026Article
- Repeat-associated ataxias in a German patient cohort analysed by targeted parallel long-read sequencing.Brain : a journal of neurology · 2026Article
- Progress and challenges in sporadic late-onset cerebellar ataxias.Nature reviews. Neurology · 2025Review
- FGF14 repeat length and mosaic interruptions: modifiers of spinocerebellar ataxia 27B?Brain : a journal of neurology · 2025Article
- GAA-FGF14 Expansions and CACNA1A Variants: Phenotypic Overlap and Diagnostic Implications.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Delineating the pathogenic threshold and phenotypic spectrum of SCA27B: findings from a large French-Canadian cohort.Journal of neurology · 2025Article
- Exploration of Neurodegenerative Diseases Using Long-Read Sequencing and Optical Genome Mapping Technologies.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- A prospective trial comparing programmable targeted long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia.Genome research · 2025Article
- High Prevalence of the Intronic GAA-Neurology. Genetics · 2025Article
Corrections and comments
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Authors and funding
28 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genome data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions. Uninterrupted AAG expansions are significantly enriched in patients with ataxia from a lower threshold (180-200 repeats) than previously reported based on expansion size alone. Conversely, AAGGAG hexameric expansions are equally frequent in patients and controls. Distinct 5' flanking regions, interruptions and pre-repeat sequences correlate with repeat size. Furthermore, pure AAG (pathogenic) and AAGGAG (non-pathogenic) repeats form different secondary structures. Regardless of expansion size, SCA27B is a recognizable clinical entity characterized by frequent episodic ataxia and downbeat nystagmus, similar to the presentation observed in a family with a previously unreported nonsense variant (SCA27A). Overall, this study suggests that SCA27B is a major overlooked cause of adult-onset ataxia, accounting for 23-31% of unsolved patients. We strongly recommend re-evaluating pathogenic thresholds and integrating expansion sequencing into the molecular diagnostic process.
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