Characterization of Novel Mutation of IDUA Gene in a Chinese Patient with Hurler Syndrome

Author: Yen-Ni Teng, Guey-Jen Lee-Chen(Department of Biology, National Taiwan Normal University), Tso-Ren Wang, Wuh-Liang Hwu(Department of Medical Genetics and Pediatrics National Taiwan University Hospital)

Vol.&No.：Vol. 45, NO. 1
Date：October 2000
Pages：1-9
DOI：10.6301/JNTNU.2000.45.01

Abstract：

DNA screening for α-L-iduronidase (IDUA) gene mutation was performed in a Chinese patient with Hurler syndrome (MPS IH). The exon-containing genomic DNA segments were amplified by polymerase chain reaction (PCR) and subjected to agarose gel electrophoresis and single-strand conformation polymorphrphism (SSCP) analysis. Aberrant PCR products or SSCP bands were cloned and sequenced to study the molecular lesions. The patient has 1447del27 (Ser453→Arg in addition to in frame deletion of codons 454-462) in one allele and 1474ins15 (in frame insertion of 5 unrelated amino acids at codon 463) in the other allele. Expression of recombinant IDUA cDNA containing 1447del27 or 1474ins15 mutation showed traced amounts of α-L-iduronidase activity compared to that of normal cDNA upon transfection into COS-7 cells. By northern blot analysis, 24% 1447del27 mRNA and 49% 1474ins15 mRNA were detected. Both 1447del27 and 1474ins15 mutations affect either synthesis or stability of IDUA protein by western blot analysis The data suggest that the1447del27 and 1474ins15 mutations result in the severe Hurler phenotype of the patient.

Keywords：Hurler syndrome, α-L-iduronidase, gene mutation

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