Journal Article

DZNE-2026-00928

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Longitudinal progression, metrics, age-dependence, and modifiers of ataxia severity in SCA27B: a multicentre study of 219 patients.

Traschütz, A. (First author)DZNE* ; Hilgers, R.-D. ; Erdlenbruch, F. ; Depienne, C. ; Wirth, T. ; Delvallée, C. ; Nümann, A. ; Ashton, C. ; Pellerin, D. ; Indelicato, E. ; Heindl, F. ; Renaud, M. ; Borsche, M. ; Grobe-Einsler, M.DZNE* ; Faber, J.DZNE* ; Klockgether, T.Extern* ; Schöls, L.DZNE* ; Brais, B. ; Anheim, M. ; Timmann, D. ; Synofzik, M. (Last author)DZNE*

2026
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ebiom.2026.106437

Abstract: Spinocerebellar Ataxia 27B (SCA27B) is a novel, frequent and likely treatable late-onset autosomal-dominant ataxia caused by GAA repeat-expansions in FGF14. For understanding disease evolution and imminent trial planning, metrics of the most widely used clinical outcome assessment (Scale for the Assessment and Rating of Ataxia/SARA), longitudinal progression and modifiers thereof are warranted.Multicentre intercontinental observational study (2015-2024) of 661 assessments from 219 patients with SCA27B (age: 68 ± 10 years; SARA: 9 ± 6 points) with item-level distribution-based analyses to characterise SARA metrics relative to ageing-related impairment in 390 healthy controls; and linear mixed-effects modelling to determine longitudinal progression and demographic or genetic modifiers.Ataxia severity in SCA27B as assessed by SARA was primarily attributable to gait, stance, and lower-limb impairment; other ataxia domains scored ≤1 SARA point in 79-94% of patients. Discrimination of SCA27B motor performance from controls decreased with age due to ageing-related motor variability captured by SARA, thus limiting potential metric response windows for symptomatic treatments. Disease progression was faster in the presence of interfering ageing-related comorbidities in 14 (6%) patients. Overall longitudinal progression of SCA27B was 0.54 SARA points/year [95% CI: 0.37-0.71]. Expansions of (GAA)> 180 repeats were frequent also on the shorter allele (n = 18 (8%), range: 196-348 repeats), and associated with faster progression (+1.6 SARA points/year, [95% CI: 0.9-2.2]), including also otherwise less affected ataxia domains speech and sitting.Disease progression in SCA27B is characterised by mild progression, ageing-related motor variabilities and comorbidities, and associated with repeat size on both alleles.Else-Kröner-Fresenius-Stiftung, EU, DFG, BMBF, CIHR, NAF, Ataxia-UK, CSC.

Keyword(s): Ataxia ; Modifiers ; Natural history ; Progression ; SCA27B ; Trials

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)
2. Clinical Research Coordination (Clinical Research (Bonn))
3. Patient Studies (Bonn) (Patient Studies (Bonn))
4. Clinical Neurogenetics (AG Schöls)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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