Identification and characterization of ‐3c–g acceptor splice site mutation in human α‐ l‐iduronidase associated with mucopolysaccharidosis type IH/S
- 1 February 2000
- journal article
- case report
- Published by Wiley in Clinical Genetics
- Vol. 57 (2) , 131-136
- https://doi.org/10.1034/j.1399-0004.2000.570207.x
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.Keywords
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