THE HUMAN CHITOTRIOSIDASE GENE - NATURE OF INHERITED ENZYME DEFICIENCY

The human chitinase, named chitotriosidase, is a member of family 18 o f glycosylhydrolases. Following the cloning of the chitotriosidase cDN A (Boot, R. G., Renkema, G. H., Strijland, A., van Zonneveld, A. J., a nd Aerts, J. M. F. G. (1995) J. Biol. Chem. 270, 26252-26256), the gen e and mRNA have been investigated. The chitotriosidase gene is assigne d to chromosome 1q31-q32. The gene consists of 12 exons and spans abou t 20 kilobases, The nature of the common deficiency in chitotriosidase activity is reported. A 24-base pair duplication in exon 10 results i n activation of a cryptic 3' splice site, generating a mRNA with an in -frame deletion of 87 nucleotides. All chitotriosidase-deficient indiv iduals tested were homozygous for the duplication. The observed carrie r frequency of about 35% indicates that the duplication is the predomi nant cause of chitotriosidase deficiency, The presence of the duplicat ion in individuals from various ethnic groups suggests that this mutat ion is relatively old.