RFC1 repeat expansions in downbeat nystagmus syndromes: frequency and phenotypic profile.
J Neurol
; 271(5): 2886-2892, 2024 May.
Article
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| MEDLINE
| ID: mdl-38381176
ABSTRACT
OBJECTIVES:
The cause of downbeat nystagmus (DBN) remains unknown in a substantial number of patients ("idiopathic"), although intronic GAA expansions in FGF14 have recently been shown to account for almost 50% of yet idiopathic cases. Here, we hypothesized that biallelic RFC1 expansions may also represent a recurrent cause of DBN syndrome.METHODS:
We genotyped the RFC1 repeat and performed in-depth phenotyping in 203 patients with DBN, including 65 patients with idiopathic DBN, 102 patients carrying an FGF14 GAA expansion, and 36 patients with presumed secondary DBN.RESULTS:
Biallelic RFC1 AAGGG expansions were identified in 15/65 patients with idiopathic DBN (23%). None of the 102 GAA-FGF14-positive patients, but 2/36 (6%) of patients with presumed secondary DBN carried biallelic RFC1 expansions. The DBN syndrome in RFC1-positive patients was characterized by additional cerebellar impairment in 100% (15/15), bilateral vestibulopathy (BVP) in 100% (15/15), and polyneuropathy in 80% (12/15) of cases. Compared to GAA-FGF14-positive and genetically unexplained patients, RFC1-positive patients had significantly more frequent neuropathic features on examination and BVP. Furthermore, vestibular function, as measured by the video head impulse test, was significantly more impaired in RFC1-positive patients.DISCUSSION:
Biallelic RFC1 expansions are a common monogenic cause of DBN syndrome.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Fenotipo
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Nistagmo Patológico
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Proteína de Replicación C
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá