Indelicato Elisabetta, Fleszar Zofia, Pellerin David, Nachbauer Wolfgang, Zuchner Stephan, Traschütz Andreas, Amprosi Matthias, Schöls Ludger, Haack Tobias B, Brais Bernard, Boesch Sylvia, Synofzik Matthis
Center for Rare Movement Disorders Innsbruck, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
Mov Disord. 2025 Aug 19. doi: 10.1002/mds.30328.
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.
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.
This is a cross-sectional multicenter study.
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.
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.
FGF14基因内含子中的（GAA）•（TTC）重复序列扩增最近被确定为脊髓小脑共济失调27B型（SCA27B）的病因，这是一种既有慢性小脑共济失调又有发作性症状的疾病。SCA27B的表型与CACNA1A谱系障碍的表型重叠。
本研究的目的是调查迄今被认为与潜在的CACNA1A变异相关的共济失调患者中GAA-FGF14重复序列扩增的患病率。
这是一项横断面多中心研究。
GAA-FGF14检测显示，在67例携带CACNA1A变异的患者中有6例（9%）存在致病性扩增（≥250次重复）。所有致病性GAA-FGF14扩增的患者发病年龄均>40岁，且在CACNA1A中携带意义未明的变异（VUS）。基因重新评估导致6例患者中有4例的CACNA1A VUS被重新分类为可能良性，这4例患者最终被诊断为SCA27B。
以前被认为与CACNA1A相关疾病的迟发性共济失调病例应重新评估并进行SCA27B检测，特别是如果与CACNA1A中的VUS相关。©2025作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森病和运动障碍协会出版。
