학술논문
Natural History and Phenotypic Spectrum of GAA‐FGF14 Sporadic Late‐Onset Cerebellar Ataxia (SCA27B).
Document Type
Article
Author
Wirth, Thomas; Clément, Guillemette; Delvallée, Clarisse; Bonnet, Céline; Bogdan, Thomas; Iosif, Andra; Schalk, Audrey; Chanson, Jean‐Baptiste; Pellerin, David; Brais, Bernard; Roth, Virginie; Wandzel, Marion; Fleury, Marie‐Céline; Piton, Amélie; Calmels, Nadège; Namer, Izzie Jacques; Kremer, Stéphane; Tranchant, Christine; Renaud, Mathilde; Anheim, Mathieu
Source
Subject
Language
ISSN
0885-3185
Abstract
Background: Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B‐MIM:620174). Whether they represent a common cause of sporadic late‐onset cerebellar ataxia (SLOCA) remains to be established. Objectives: To estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients. Methods: FGF14 expansions screening combined with longitudinal deep‐phenotyping in a prospective cohort of 118 SLOCA patients (onset >40 years of age, no family history of cerebellar ataxia) without a definite diagnosis. Results: Prevalence of SCA27B was 12.7% (15/118). Higher age of onset, higher Spinocerebellar Degeneration Functional Score, presence of vertigo, diplopia, nystagmus, orthostatic hypotension absence, and sensorimotor neuropathy were significantly associated with SCA27B. Ataxia progression was ≈0.4 points per year on the Scale for Assessment and Rating of Ataxia. Conclusions: FGF14 expansion is a major cause of SLOCA. Our natural history data will inform future FGF14 clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]