Similarities and differences in the phenotype, genotype and pathogenesis of different spinocerebellar ataxias.
Historically, the differential diagnosis of the autosomal ataxias (ADCAs) has been difficult. In 1983 Harding proposed a useful clinical classification. Since 1983 ADCAs have been increasingly characterized in terms of their genetic locus and are referred to as spinocerebeller ataxia (SCA). The overlap between the SCA phenotypes and the high variability within SCA subgroups means that, for individual patients, the underlying mutation cannot be predicted reliable purely on the basis of clinical symptoms and so diagnosis should be made on the genotype. However, for executing DNA analyses in order of clinical likelihood, neurologists may try to deduce the underlying mutation by using a clinical algorithm. In this article we not only describe such an algorithm but also plot the pathway from clinical presentation, genetic classification and mutation, abnormal protein to common neuropathology in these disorders.
Schelhaas
H J
HJ
Department of Neurology, Medisch Spectrum Twente, Enschede, The Netherlands. H.J.Schelhaas@A1.nl
Ippel
P F
PF
Beemer
F A
FA
Hageman
G
G
D005838:Genotype; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000502:physiology; D010641:Phenotype; D012091:Repetitive Sequences, Nucleic Acid; D020754:Spinocerebellar Ataxias / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D018911:Trinucleotide Repeats
D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine