Article

Molecular genetic studies in the past decade have demonstrated the enormous genetic heterogeneity among the dominantly inherited ataxias. Mutations at several distinc loci give rise to the progressive dominant ataxias and at least 2 different mutations cause episodic ataxias with dominant inheritance. The well established egenotypes for progressive dominant ataxias have all involved expansions of repeated CAG sequences. Clinically these patients present with progressive cerebellar deficits as wells as signs relating to pathology in other neural systems in a variable type, but the identification of the genotyp from the clinical phenotype alone is usually difficult. The CAG expansions involved usually are unstable with intergenerational expansions as wells as contractions of the repeat size. Phenotypic features such as age of onset and to a lesser extent disease progression rate and the presence of specific clinical signs depend on the CAG repeat size. Identification of the mutations has allowed precise genotypic diagnosis in several families allowing more accurate genetic counseling, including predictive testing of at risk individuals when sought. Also, increasing information about the gene products and their abnormal distributions in disease brain is rapidly giving rise to rational ideas about the pathogenesis of neuronal degeneration in these diseases and raising hope for meaningful treatment strategies.

Langue : ANGLAIS

Tiré à part : OUI

Identifiant basis : 2000213320