LCR-initiated rearrangements at the IDS locus, completed with Alu-mediated recombination or non-homologous end joining

Junko Oshima, Jennifer A. Lee, Amy M. Breman, Priscilla H. Fernandes, Dusica Babovic-Vuksanovic, Patricia A. Ward, Lynne A. Wolfe, Christine M. Eng, Daniela Del Gaudio

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3 Scopus citations

Abstract

Mucopolysaccharidosis type II (MPS II) is caused by mutations in the IDS gene, which encodes the lysosomal enzyme iduronate-2-sulfatase. In ∼20% of MPS II patients the disorder is caused by gross IDS structural rearrangements. We identified two male cases harboring complex rearrangements involving the IDS gene and the nearby pseudogene, IDSP1, which has been annotated as a low-copy repeat (LCR). In both cases the rearrangement included a partial deletion of IDS and an inverted insertion of the neighboring region. In silico analyses revealed the presence of repetitive elements as well as LCRs at the junctions of rearrangements. Our models illustrate two alternative consequences of rearrangements initiated by non-allelic homologous recombination of LCRs: resolution by a second recombination event (that is, Alu-mediated recombination), or resolution by non-homologous end joining repair. These complex rearrangements have the potential to be recurrent and may be present among those MSP II cases with previously uncharacterized aberrations involving IDS.

Original languageEnglish (US)
Pages (from-to)516-523
Number of pages8
JournalJournal of Human Genetics
Volume56
Issue number7
DOIs
StatePublished - Jul 1 2011

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Keywords

  • Hunter syndrome
  • X-linked diseases
  • array CGH
  • chromosomal rearrangements
  • clinical molecular genetics
  • lysosomal storage diseases
  • mucopolysaccharidoses

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Oshima, J., Lee, J. A., Breman, A. M., Fernandes, P. H., Babovic-Vuksanovic, D., Ward, P. A., Wolfe, L. A., Eng, C. M., & Del Gaudio, D. (2011). LCR-initiated rearrangements at the IDS locus, completed with Alu-mediated recombination or non-homologous end joining. Journal of Human Genetics, 56(7), 516-523. https://doi.org/10.1038/jhg.2011.51