DNA deletion confined to the iduronate-2-sulfatase promoter abolishes IDS gene expression.

TitleDNA deletion confined to the iduronate-2-sulfatase promoter abolishes IDS gene expression.
Publication TypeJournal Article
Year of Publication1998
AuthorsTimms, KM, Huckett, LE, Belmont, JW, Shapira, SK, Gibbs, RA
JournalHum Mutat
Date Published1998
KeywordsBase Sequence, Child, Preschool, DNA Mutational Analysis, Gene Expression Regulation, Humans, Iduronate Sulfatase, Male, Molecular Sequence Data, Mucopolysaccharidosis II, Pedigree, Phenotype, Promoter Regions, Genetic, Sequence Analysis, DNA, Sequence Deletion

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.

Alternate JournalHum Mutat
PubMed ID9482575
Grant ListP30 HG00210 / HG / NHGRI NIH HHS / United States
R01 HG00823 / HG / NHGRI NIH HHS / United States

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