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Identification of 6 new mutations in the iduronate sulfatase gene
Author(s) -
Vallance Hilary D.,
Bernard Lynn,
Rashed Michael,
Chiu Doris,
Le Grace,
Toone Jenny,
Applegarth Derek A.,
CoulterMackie Marion
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1999)13:4<338::aid-humu15>3.0.co;2-3
Subject(s) - missense mutation , biology , hunter syndrome , genetics , mucopolysaccharidosis type ii , splice site mutation , gene , phenotype , mutation , microbiology and biotechnology , rna splicing , enzyme replacement therapy , disease , rna , medicine
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. © 1999 Wiley‐Liss, Inc.