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. 2023 Dec;30(12):3828-3833.
doi: 10.1111/ene.16039. Epub 2023 Aug 27.

Frequency and phenotypic spectrum of spinocerebellar ataxia 27B and other genetic ataxias in a Spanish cohort of late-onset cerebellar ataxia

Pablo Iruzubieta  1   2   3 , David Pellerin  3   4 , Alberto Bergareche  1   2 , Inés Albajar  1 , Elisabet Mondragón  1   2 , Ana Vinagre  1   2 , Roberto Fernández-Torrón  1   2 , Fermín Moreno  1   2 , Jon Equiza  1 , David Campo-Caballero  1 , Juan José Poza  1 , Marta Ruibal  1 , Alessandro Formica  1 , Marie-Josée Dicaire  4 , Matt C Danzi  5 , Stephan Zuchner  5 , Ioana Croitoru  2 , Montserrat Ruiz  6   7 , Agatha Schlüter  6   7 , Carlos Casasnovas  6   8 , Aurora Pujol  6   7   9 , Bernard Brais  4   10 , Henry Houlden  3 , Adolfo López de Munain  1   2 , Javier Ruiz-Martínez  1   2
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Free article

Frequency and phenotypic spectrum of spinocerebellar ataxia 27B and other genetic ataxias in a Spanish cohort of late-onset cerebellar ataxia

Pablo Iruzubieta et al. Eur J Neurol. 2023 Dec.
Free article

Abstract

Background and purpose: Dominantly inherited GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene have recently been shown to cause spinocerebellar ataxia 27B (SCA27B). We aimed to study the frequency and phenotype of SCA27B in a cohort of patients with unsolved late-onset cerebellar ataxia (LOCA). We also assessed the frequency of SCA27B relative to other genetically defined LOCAs.

Methods: We recruited a consecutive series of 107 patients with LOCA, of whom 64 remained genetically undiagnosed. We screened these 64 patients for the FGF14 GAA repeat expansion. We next analysed the frequency of SCA27B relative to other genetically defined forms of LOCA in the cohort of 107 patients.

Results: Eighteen of 64 patients (28%) carried an FGF14 (GAA)≥250 expansion. The median (range) age at onset was 62.5 (39-72) years. The most common clinical features included gait ataxia (100%) and mild cerebellar dysarthria (67%). In addition, episodic symptoms and downbeat nystagmus were present in 39% (7/18) and 37% (6/16) of patients, respectively. SCA27B was the most common cause of LOCA in our cohort (17%, 18/107). Among patients with genetically defined LOCA, SCA27B was the main cause of pure ataxia, RFC1-related disease of ataxia with neuropathy, and SPG7 of ataxia with spasticity.

Conclusion: We showed that SCA27B is the most common cause of LOCA in our cohort. Our results support the use of FGF14 GAA repeat expansion screening as a first-tier genetic test in patients with LOCA.

Keywords: FGF14; GAA-FGF14 ataxia; RFC1; SCA27B; ataxia; late-onset cerebellar ataxia; neurogenetics; repeat expansion disorder.

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References

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