THE MOLECULAR DEFECT UNDERLYING CANINE FUCOSIDOSIS

Fucosidosis is a lysosomal storage disease which affects humans and En glish springer spaniel dogs. The disease is recessively inherited in b oth species and results from a deficiency of the enzyme alpha-L-fucosi dase. We have recently cloned and sequenced the canine fucosidase gene (EMBL sequence admission number X92448 (cDNA) and X92671-X92678 (indi vidual exonic data)). The gene spans 12 kb and consists of eight exons . SSCP based mutation analysis of affected animals was carried out on the coding region of this gene both with exonic primers, and intronic primer pairs for each exon. A 14 base pair deletion of the cDNA was id entified at the 3' end of exon 1 in fucosidosis affected animals. Surp risingly, PCR based genomic cloning of DNA from these animals showed a n identical deletion in this DNA, ending at the start of intron 1. Thi s change causes a frameshift and, in consequence, 25 novel codons are transcribed in exon 2 before the first of two adjacent premature stop codons is encountered.