PMID- 10220152
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20191103
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 13
IP  - 4
DP  - 1999
TI  - Identification of 6 new mutations in the iduronate sulfatase gene. Mutation in
      brief no. 233. Online.
PG  - 338
AB  - Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage 
      disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. We sequenced
      genomic DNA and RT-PCR products in the iduronate sulfatase (IDS) gene in 6
      unrelated patients with Hunter syndrome to assess genotype/phenotype
      relationships and offer carrier testing where required. Six novel mutations were 
      identified: four missense mutations, one four-base pair deletion (596-599delAACA)
      and a cryptic splice site mutation. Three of the missense mutations were
      significant amino acid substitutions (S143F, S491F, E341K) of which the latter
      two involve amino acids conserved amongst sulfatase enzymes. The patients
      identified with these mutations all had a severe clinical phenotype. One missense
      mutation with a minimal amino acid substitution (H342Y), in a non-conserved
      region of the gene, was associated with a mild clinical phenotype. We identified 
      a novel cryptic splice site (IVS5+934G>A) with some normal (wild type) mRNA
      processing. We predict that the normal mRNA product confered some residual
      functional enzyme, resulting in a mild phenotype associated with the absence of
      overt central nervous system disease.
FAU - Vallance, H D
AU  - Vallance HD
AD  - Department of Pathology, University of British Columbia, Vancouver, Canada.
      hvallance@wpog.childhosp.bc.ca
FAU - Bernard, L
AU  - Bernard L
FAU - Rashed, M
AU  - Rashed M
FAU - Chiu, D
AU  - Chiu D
FAU - Le, G
AU  - Le G
FAU - Toone, J
AU  - Toone J
FAU - Applegarth, D A
AU  - Applegarth DA
FAU - Coulter-Mackie, M
AU  - Coulter-Mackie M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (RNA, Messenger)
RN  - EC 3.1.6.13 (Iduronate Sulfatase)
SB  - IM
MH  - Gene Deletion
MH  - Genotype
MH  - Humans
MH  - Iduronate Sulfatase/*genetics
MH  - Mucopolysaccharidosis II/genetics
MH  - Mutation, Missense
MH  - Phenotype
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Analysis, DNA
EDAT- 1999/04/29 02:03
MHDA- 2000/06/22 10:00
CRDT- 1999/04/29 02:03
PHST- 1999/04/29 02:03 [pubmed]
PHST- 2000/06/22 10:00 [medline]
PHST- 1999/04/29 02:03 [entrez]
AID - 10.1002/(SICI)1098-1004(1999)13:4<338::AID-HUMU15>3.0.CO;2-3 [pii]
AID - 10.1002/(sici)1098-1004(1999)13:4<338::aid-humu15>3.0.co;2-3 [doi]
PST - ppublish
SO  - Hum Mutat. 1999;13(4):338. doi:
      10.1002/(sici)1098-1004(1999)13:4<338::aid-humu15>3.0.co;2-3.