PMID- 10466419
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20061115
IS  - 0009-9163 (Print)
IS  - 0009-9163 (Linking)
VI  - 56
IP  - 1
DP  - 1999 Jul
TI  - Mucopolysaccharidosis type I: characterization of novel mutations affecting
      alpha-L-iduronidase activity.
PG  - 66-70
AB  - alpha-L-Iduronidase (IDUA) deficiency (mucopolysaccharidosis type I, MPS I)
      involves a broad spectrum of clinical severity ranging from a severe Hurler
      syndrome through an intermediate Hurler Scheie syndrome to a mild Scheie
      syndrome. To date, a number of mutations of the IDUA gene are known in Hurler
      syndrome, but only a few in Hurler Scheie or Scheie syndrome. The
      characterization of novel mutations in two patients with the Hurler-Scheie
      syndrome is reported on. The novel R619G mutation (C-G transversion in codon 619)
      was apparently homozygous. In transfected COS-7 cells, R619G caused significant
      reduction in enzyme activity (1.5% of normal activity), although it did not cause
      significant reduction in IDUA mRNA or protein level. Conversely, the previously
      described homozygous T364M mutation (C-T transition in codon 364) caused a
      decrease in the level of IDUA mRNA. Studies inhibiting RNA synthesis with
      actinomycin D or inhibiting protein synthesis with cycloheximide demonstrate that
      the decrease in the latter mutation is attributable to an increased rate of mRNA 
      decay. By examining the stability of IDUA mRNA and protein, studies provide
      better insight into the effect of mutation on IDUA activity.
FAU - Lee-Chen, G J
AU  - Lee-Chen GJ
AD  - Department of Biology, National Taiwan Normal University, Taipei, ROC.
      t43019@cc.ntnu.edu.tw
FAU - Lin, S P
AU  - Lin SP
FAU - Tang, Y F
AU  - Tang YF
FAU - Chin, Y W
AU  - Chin YW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Clin Genet
JT  - Clinical genetics
JID - 0253664
RN  - 0 (DNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - EC 3.2.1.76 (Iduronidase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Northern
MH  - COS Cells
MH  - Catalysis
MH  - DNA, Complementary
MH  - Enzyme Stability
MH  - Humans
MH  - Iduronidase/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Mucopolysaccharidosis I/enzymology/*genetics
MH  - *Mutation
MH  - RNA, Messenger/genetics/metabolism
EDAT- 1999/08/31 00:00
MHDA- 1999/08/31 00:01
CRDT- 1999/08/31 00:00
PHST- 1999/08/31 00:00 [pubmed]
PHST- 1999/08/31 00:01 [medline]
PHST- 1999/08/31 00:00 [entrez]
PST - ppublish
SO  - Clin Genet. 1999 Jul;56(1):66-70.