The etiology of most recessive cerebellar ataxias is unknown. We have recently identified a novel ataxia gene, ATCAY/Atcay, for Ataxia, Cayman type. Mutations in this gene cause recessive ataxia in mouse (alleles of jittery) and human (Cayman Ataxia). The jittery phenotypes range from a barely detectable hesitant, slightly ataxic walk with normal life span in a mild allele to severe ataxia, dystonia with seizures and early death in other alleles. Cayman Ataxia is a recessive ataxia found so far exclusively on one region of Grand Cayman island where it arose by founder effect. Cayman Ataxia patients show severe truncal ataxia, ocular movement abnormalities, and mental retardation. We will identify all causal mutations in mouse and determine which of two mutations that are present in all Cayman Ataxia patients causes the disorder. ? ? The protein, CAYTAXIN, is expressed at high levels exclusively in neuronal tissues, including brain, spinal and enteric ganglion cells. The C-terminal end of the protein has a CRAL-TRIO domain which is typical for proteins that bind or transport small molecules. The C-terminus is also homologous to a BCH (BNIP2-CDC42GAP homology) domain present in CDC42GAP-like proteins. To characterize the functions of this protein, we will study its expression, the intracellular localization of the protein, its interacting proteins and its potential functions in apoptosis and/or signalling. Our studies may reveal a novel pathway to the etiology of ataxia. ? ?
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