The most frequent subtype of autosomal dominant inherited spinocerebellar ataxias is caused by CAG repeat expansions of more than 55 units in the ataxin-3 gene. The clinical variability of the phenotype depends on the length of the expanded repeat and the age at onset (and thus indirectly with the repeat size). Anticipation of the phenotype is most frequently associated with repeat expansions in paternal transmission. In this review we describe four clinical subphenotypes and correlate them to the respective repeat expansions. We also provide a detailed description of the neuropathological features. Finally, we discuss the current knowledge on the function of normal and dysfunction of altered ataxin-3 and how this translates to the predicted structure of the protein.
SCA3: Neurological features, pathogenesis and animal models
PASTORE A;
2008
Abstract
The most frequent subtype of autosomal dominant inherited spinocerebellar ataxias is caused by CAG repeat expansions of more than 55 units in the ataxin-3 gene. The clinical variability of the phenotype depends on the length of the expanded repeat and the age at onset (and thus indirectly with the repeat size). Anticipation of the phenotype is most frequently associated with repeat expansions in paternal transmission. In this review we describe four clinical subphenotypes and correlate them to the respective repeat expansions. We also provide a detailed description of the neuropathological features. Finally, we discuss the current knowledge on the function of normal and dysfunction of altered ataxin-3 and how this translates to the predicted structure of the protein.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
