title: Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S.
abstract: DNA screening for mutations in the alpha-L-iduronidase (IDUA) gene was performed in a Chinese mucopolysaccharidosis type IH/S patient. The patient had two different mutations: the maternal allele has L346R (t-g transversion in codon 346) and the paternal allele has 388-3c-g (c-g transversion at position -3 of the 3' splice site of intron 2). In transfected COS-7 cells, L346R showed no appreciable IDUA activity (0.4% of normal activity), although it did not cause an apparent reduction in IDUA mRNA or protein level. The 388-3c-g mutation profoundly affects normal splicing leading to a very unstable mRNA. Expression of the IDUA cDNA containing the mutated acceptor splice site showed trace amounts of enzyme activity (1.6% of normal activity). The results provide further support for the importance of cytosine at the -3 position in RNA processing.
authors.affiliation: Department of Biology, National Taiwan Normal University, Taipei, ROC.
authors.forename: Y N
authors.initials: YN
authors.lastname: Teng
authors.forename: T R
authors.initials: TR
authors.lastname: Wang
authors.forename: W L
authors.initials: WL
authors.lastname: Hwu
authors.forename: S P
authors.initials: SP
authors.lastname: Lin
authors.forename: G J
authors.initials: GJ
authors.lastname: Lee-Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D002648:Child; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007068:Iduronidase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D008059:Mucopolysaccharidosis I / Q000235:genetics*; D009154:Mutation; D010957:Plasmids; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D007068:Iduronidase