Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: An intronic (GAA)•(TTC) repeat expansion in FGF14 was recently identified as the cause of spinocerebellar ataxia 27B (SCA27B), a disorder presenting with both chronic cerebellar ataxia and episodic symptoms. The phenotype of SCA27B overlaps with that of CACNA1A spectrum disorders.
Objective: The objective of this work was to investigate the prevalence of GAA-FGF14 repeat expansions in patients with ataxia so far considered to be related to underlying CACNA1A variants.
Methods: This is a cross-sectional multicenter study.
Results: GAA-FGF14 testing showed pathogenic expansions (≥250 repeats) in 6/67 (9%) patients carrying CACNA1A variants. All patients with a pathogenic GAA-FGF14 expansion had a disease onset >40 years and carried variants of uncertain significance (VUSs) in CACNA1A. Genetic reevaluation led to the reclassification of CACNA1A VUSs as likely benign in four of six patients, who were ultimately diagnosed with SCA27B.
Conclusions: Late-onset ataxia cases previously considered as CACNA1A-related disorder should be reevaluated and tested for SCA27B, particularly if related to a VUS in CACNA1A. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/mds.30328 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Altered Gating of Two Ca2.1 Variants Linked to Neurodevelopmental Disorders With Epilepsy and Migraine.
FASEB J
September 2025
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
P/Q-type (Ca2.1) Ca channels regulate the release of neurotransmitter at central synapses. Missense and nonsense mutations in CACNA1A, the gene that encodes the principal α subunit of the Ca2.
View Article and Find Full Text PDFGenetic Insights into Hemiplegic Migraine: Whole Exome Sequencing Highlights Vascular Pathway Involvement via Association Analysis.
Genes (Basel)
July 2025
Genomics Research Centre, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia.
: Hemiplegic migraine (HM) is a rare and severe subtype of migraine with a complex genetic basis. Although pathogenic variants in , , and explain some familial cases, a significant proportion of patients remain genetically undiagnosed. Increasing evidence points to an overlap between migraine and cerebral small vessel disease (SVD), implicating vascular dysfunction in HM pathophysiology.
View Article and Find Full Text PDFGenetic Variants and Their Potential Involvement in Migraine Pathogenesis.
Int J Mol Sci
August 2025
Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland.
Migraine is a prevalent neurological disorder that affects over 1 billion individuals worldwide. The pathogenesis of migraine remains incompletely understood, though evidence suggests a multifactorial etiology involving genetic factors. The gene has been implicated in rare forms of Familial Hemiplegic Migraine (FHM).
View Article and Find Full Text PDFGAA-FGF14 Expansions and CACNA1A Variants: Phenotypic Overlap and Diagnostic Implications.
Mov Disord
August 2025
German Center for Neurodegenerative Diseases, Tübingen, Germany.
Background: An intronic (GAA)•(TTC) repeat expansion in FGF14 was recently identified as the cause of spinocerebellar ataxia 27B (SCA27B), a disorder presenting with both chronic cerebellar ataxia and episodic symptoms. The phenotype of SCA27B overlaps with that of CACNA1A spectrum disorders.
Objective: The objective of this work was to investigate the prevalence of GAA-FGF14 repeat expansions in patients with ataxia so far considered to be related to underlying CACNA1A variants.
Comprehensive identification of pathogenic tandem repeat expansions in sporadic amyotrophic lateral sclerosis: advantages of long-read vs. short-read sequencing.
Exp Biol Med (Maywood)
August 2025
Perron Institute for Neurological and Translational Science, Perth, WA, Australia.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder presenting progressive weakness of the bulbar and extremity muscles, leading to a wide-ranging clinical phenotype. More than 30 genes have been associated to genetically inherited ALS yet, approximately 85%-90% of ALS cases are sporadic. Short tandem repeats expansions, have recently been found in clinically diagnosed ALS patients and are currently investigated as potential genetic biomarkers.
View Article and Find Full Text PDF