title: The human chitotriosidase gene. Nature of inherited enzyme deficiency.
abstract: The human chitinase, named chitotriosidase, is a member of family 18 of glycosylhydrolases. Following the cloning of the chitotriosidase cDNA (Boot, R. G., Renkema, G. H., Strijland, A., van Zonneveld, A. J., and Aerts, J. M. F. G. (1995) J. Biol. Chem. 270, 26252-26256), the gene and mRNA have been investigated. The chitotriosidase gene is assigned to chromosome 1q31-q32. The gene consists of 12 exons and spans about 20 kilobases. The nature of the common deficiency in chitotriosidase activity is reported. A 24-base pair duplication in exon 10 results in activation of a cryptic 3' splice site, generating a mRNA with an in-frame deletion of 87 nucleotides. All chitotriosidase-deficient individuals tested were homozygous for the duplication. The observed carrier frequency of about 35% indicates that the duplication is the predominant cause of chitotriosidase deficiency. The presence of the duplication in individuals from various ethnic groups suggests that this mutation is relatively old.
authors.affiliation: Department of Biochemistry, University of Amsterdam, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: R G
authors.initials: RG
authors.lastname: Boot
authors.forename: G H
authors.initials: GH
authors.lastname: Renkema
authors.forename: M
authors.initials: M
authors.lastname: Verhoek
authors.forename: A
authors.initials: A
authors.lastname: Strijland
authors.forename: J
authors.initials: J
authors.lastname: Bliek
authors.forename: T M
authors.initials: TM
authors.lastname: de Meulemeester
authors.forename: M M
authors.initials: MM
authors.lastname: Mannens
authors.forename: J M
authors.initials: JM
authors.lastname: Aerts
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005838:Genotype; D006596:Hexosaminidases / Q000172:deficiency / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D017403:In Situ Hybridization; D008264:Macrophages / Q000201:enzymology; D008969:Molecular Sequence Data; D009426:Netherlands / Q000208:ethnology; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D006596:Hexosaminidases; C086400:chitotriosidase