Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar deficits.
Ann Neurol
; 54(6): 725-31, 2003 Dec.
Article
em En
| MEDLINE
| ID: mdl-14681882
ABSTRACT
Episodic ataxia type 2 (EA2) is a dominantly inherited disorder, characterized by spells of ataxia, dysarthria, vertigo, and migraines, associated with mutations in the neuronal calcium-channel gene CACNA1A. Ataxic spells lasting minutes to hours are provoked by stress, exercise, or alcohol. Some patients exhibit nystagmus between spells and some develop progressive ataxia later in life. At least 21 distinct CACNA1A mutations have been identified in EA2. The clinical and genetic complexities of EA2 have offered few insights into the underlying pathogenic mechanisms for this disorder. We identified a novel EA2 kindred in which members had ataxic spells induced by fevers or high environmental temperature. We identified a novel CACNA1A mutation (nucleotides 1253+1 G-->A) that was present in all subjects with febrile spells or ataxia. Moreover, we found that, regardless of age or interictal clinical status, all affected subjects had objective evidence of abnormal saccades, ocular fixation, and postural stability. These findings suggest that early cerebellar dysfunction in EA2 results from the intrinsically abnormal properties of the CACNA1A channel rather than a degenerative process.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio
/
Ataxia Cerebelar
/
Convulsões Febris
/
Mutação
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child, preschool
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article