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DNA deletion confined to the iduronate‐2‐sulfatase promoter abolishes IDS gene expression
Author(s) -
Timms Kirsten M.,
Huckett Louise E.,
Belmont John W.,
Shapira Stuart K.,
Gibbs Richard A.
Publication year - 1998
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(1998)11:2<121::aid-humu4>3.0.co;2-m
Subject(s) - biology , exon , genetics , gene , microbiology and biotechnology , hunter syndrome , intron , point mutation , mutation
Deficiency of the enzyme iduronate‐2‐sulfatase (IDS) results in Hunter syndrome, an X‐linked recessive lysosomal storage disorder. In this study, analysis of a patient with features of moderate to severe Hunter syndrome identified a 178‐bp deletion upstream of IDS exon 1 spanning a predicted promoter element. Sequencing of all nine IDS exons from this patient failed to identify any additional mutations within the coding regions or in intron‐exon boundaries. The 178‐bp deletion is flanked by two 13‐bp direct repeats and potential DNA topoisomerase II recognition sites. These findings point toward nonhomologous recombination as a possible mechanism for this mutation. Expression studies on this patient do not detect any IDS transcripts, indicating that the deletion spans sequences essential for IDS expression. Complete lack of expression of IDS is consistent with the moderate to severe phenotype observed in this patient. Hum Mutat 11:121–126, 1998. © 1998 Wiley‐Liss, Inc.