title: Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology.
abstract: Major advances have been made in the understanding of autosomal dominant cerebellar ataxias since genetic markers came into use in the 1980s. The subsequent mapping of nine genes, six of which have been identified, involved in this clinically diverse group of disorders highlighted their great genetic heterogeneity. Evidence is now accumulating that, except for SCA8, the same molecular and physiopathological processes underlie these diseases and other neurodegenerative disorders sharing the same mutational basis, the expansion of a (CAG)n-polyglutamine coding sequence. The clinical overlap among the different genetic entities makes prediction of the molecular origin impossible in a single patient so that molecular characterisation is necessary. However, extended clinical and neuropathological comparisons have shown that each genetic entity has a characteristic constellation of signs and symptoms that are related to CAG repeat size and disease duration. The combined genetic and clinical information form the basis of a new classification that will aid better understanding of disease evolution, assure follow up and permit genetic counselling by the clinician.
authors.affiliation: INSERM U289, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Stevanin
authors.forename: A
authors.initials: A
authors.lastname: Dürr
authors.forename: A
authors.initials: A
authors.lastname: Brice
mesh_terms: D020132:Anticipation, Genetic; D001921:Brain / Q000473:pathology; D002524:Cerebellar Ataxia / Q000145:classification / Q000235:genetics / Q000473:pathology; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D009154:Mutation; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000473:pathology; D019680:Trinucleotide Repeat Expansion
chemical_list: D010455:Peptides; C097188:polyglutamine