La céroïde-lipofuscinose de l'American Staffordshire Terriers

Abstract

Neuronal ceroid lipofuscinoses (NCLs) represent a group of inherited progressive encephalopathies characterized by progressive loss of vision, mental or motor deterioration, epileptic seizures and premature death. A spontaneous canine model of adult American Staffordshire Terriers developing an autosomal recessive NCL has been described. Through a combined genome-wide association and linkage study, a worldwide breed-specific variant in the arylsulfatase G (ARSG) gene was identified. ARSG encodes a lysosomal sulfatase. The variant causes a non-conservative amino-acid substitution in the protein. The missense substitution leads to a 75% sulfatase activity decrease in leucocytes from affected dogs. These results unravel the key role played by ARSG in NCL and neuronal homeostasis and suggest that sulfatase activity might be evaluated in human patients affected by late-onset forms of NCL. Further, a canine genomic predictive DNA-test has been developed to serve the future of the breed.