The FGF14GAA repeat expansion in Greek patients with late‐onset cerebellar ataxia and an overview of the SCA27B phenotype across populations

Author:

Kartanou Chrisoula1,Mitrousias Alexandros1,Pellerin David23,Kontogeorgiou Zoi1,Iruzubieta Pablo345,Dicaire Marie‐Josée2,Danzi Matt C.6,Koniari Chrysoula1,Athanassopoulos Konstantinos1,Panas Marios1,Stefanis Leonidas7,Zuchner Stephan6,Brais Bernard28,Houlden Henry3,Karadima Georgia1,Koutsis Georgios1

Affiliation:

1. Neurogenetics Unit, 1st Department of Neurology National and Kapodistrian University of Athens, Eginitio Hospital Athens Greece

2. Department of Neurology and Neurosurgery Montreal Neurological Hospital and Institute, McGill University Montreal Québec Canada

3. Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology London and The National Hospital for Neurology and Neurosurgery, University College London London UK

4. Department of Neurology Donostia University Hospital, Biogipuzkoa Health Research Institute Donostia‐San Sebastián Spain

5. CIBERNED Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas‐Instituto de Salud Carlos III (CIBER‐CIBERNED‐ISCIII) Madrid Spain

6. Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine Miami Florida USA

7. 1st Department of Neurology National and Kapodistrian University of Athens, Eginitio Hospital Athens Greece

8. Department of Human Genetics McGill University Montreal Québec Canada

Abstract

AbstractA pathogenic GAA repeat expansion in the first intron of the fibroblast growth factor 14 gene (FGF14) has been recently identified as the cause of spinocerebellar ataxia 27B (SCA27B). We herein screened 160 Greek index cases with late‐onset cerebellar ataxia (LOCA) for FGF14 repeat expansions using a combination of long‐range PCR and bidirectional repeat‐primed PCRs. We identified 19 index cases (12%) carrying a pathogenic FGF14 GAA expansion, a diagnostic yield higher than that of previously screened repeat‐expansion ataxias in Greek LOCA patients. The age at onset of SCA27B patients was 60.5 ± 12.3 years (range, 34–80). Episodic onset (37%), downbeat nystagmus (32%) and vertigo (26%) were significantly more frequent in FGF14 expansion‐positive cases compared to expansion‐negative cases. Beyond typical cerebellar signs, SCA27B patients often displayed hyperreflexia (47%) and reduced vibration sense in the lower extremities (42%). The frequency and phenotypic profile of SCA27B in Greek patients was similar to most other previously studied populations. We conclude that FGF14 GAA repeat expansions are the commonest known genetic cause of LOCA in the Greek population and recommend prioritizing testing for FGF14 expansions in the diagnostic algorithm of patients with LOCA.

Publisher

Wiley

Subject

Genetics (clinical),Genetics

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