title: Spinocerebellar ataxia with axonal neuropathy.
abstract: Spinocerebellar ataxia with axonal neuropathy (SCAN 1) is an autosomal recessive disorder caused by a specific point mutation (c.1478A>G, p.H493R) in the tyrosyl-DNA phosphodiesterase (TDP1) gene. Functional and genetic studies suggest that this mutation, which disrupts the active site of the Tdp1 enzyme, causes disease by a combination of decreased catalytic activity and stabilization of the normally transient covalent Tdp1-DNA intermediate. This covalent reaction intermediate can form during the repair of stalled topoisomerase I-DNA adducts or oxidatively damaged bases at the 3' end of the DNA at a strand break. However, our current understanding of the biology of Tdp1 function in humans is limited and does not allow us to fully elucidate the disease mechanism.
authors.affiliation: Department of Medical Genetics, Provincial Medical Genetics Program, Child and Family Research Institute, Children's and Women's Health Centre of British Columbia, University of British Columbia Vancouver, British Columbia, Canada.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Walton
authors.forename: Heidrun
authors.initials: H
authors.lastname: Interthal
authors.forename: Ryuki
authors.initials: R
authors.lastname: Hirano
authors.forename: Mustafa A M
authors.initials: MA
authors.lastname: Salih
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takashima
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
mesh_terms: D025063:Chromosome Disorders / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D053960:DNA Breaks; D004260:DNA Repair / Q000235:genetics; D049914:DNA Repair-Deficiency Disorders / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D020754:Spinocerebellar Ataxias / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D004247:DNA; D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human; D004264:DNA Topoisomerases, Type I