Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology.
Eur J Hum Genet. 2000-01-01; 8(1): 4-18
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1. Eur J Hum Genet. 2000 Jan;8(1):4-18.
Clinical and molecular advances in autosomal dominant cerebellar ataxias: from
genotype to phenotype and physiopathology.
Stevanin G(1), Dürr A, Brice A.
(1)INSERM U289, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
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
PMID: 10713882 [Indexed for MEDLINE]