CLONING, EXPRESSION AND CHROMOSOMAL MAPPING OF HUMAN LYSOSOMAL SIALIDASE AND CHARACTERIZATION OF MUTATIONS IN SIALIDOSIS

Sialidase (neuraminidase, EC 3.2.1.18) catalyses the hydrolysis of ter minal sialic acid residues of glyconjugates. Sialidase has been well s tudied in viruses and bacteria where it destroys the sialic acid-conta ining receptors at the surface of host cells(1-3), and mobilizes bacte rial nutrients(4). In mammals, three types of sialidases, lysosomal, p lasma membrane and cytosolic, have been described(5-7). For lysosomal sialidase in humans, the primary genetic deficiency results in an auto somal recessive disease, sialidosis, associated with tissue accumulati on and urinary excretion of sialylated oligosaccharides and glycolipid s. Sialidosis includes two main clinical variants: late-onset, sialido sis type I, characterized by bilateral macular cherry-red spots and my oclonus(8,9), and infantile-onset, sialidosis type II, characterized b y skeletal dysplasia, mental retardation and hepatosplenomegaly(10-12) . We report the identification of human lysosomal sialidase cDNA, its cloning, sequencing and expression. Examination of six sialidosis pati ents revealed three mutations, one frameshift insertion and two missen se. We mapped the lysosomal sialidase gene to human chromosome 6 (6p21 .3), which is consistent with the previous chromosomal assignment of t his gene in proximity to the HLA locus.