title: Novel type of genetic rearrangement in the iduronate-2-sulfatase (IDS) gene involving deletion, duplications, and inversions.
abstract: We describe a novel type of complex genetic rearrangement in the iduronate-2-sulfatase (IDS) gene of a severely affected MPSII patient. Southern blot analysis indicated an intragenic deletion of exons 5 and 6. The deletion spans 5,581 bp. Sequencing of the deletion junctions revealed a complex rearrangement involving duplications and inversions. A remaining 20 bp fragment (c) from the intron 6 sequence and two duplicated IDS gene fragments of 314 bp (a) from intron 6/exon 7 boundary and 23 bp (b) from exon 7 were found between the deletion breakpoints. Fragments a and c were placed in an inverted orientation. We suggest that the described rearrangement is a result of a nonhomologous recombination event at sites with little homology. The proposed model explaining this recombinational event involves the formation of "tetra-loop" single-stranded DNA structure during replication. The complexity of the described rearrangement and the lack of large homologous sequences at the mutational breakpoints suggest that complex molecular intermediates are formed during illegitimate recombination.
authors.affiliation: Section of Medical Genetics, Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Karsten
authors.forename: E
authors.initials: E
authors.lastname: Voskoboeva
authors.forename: X
authors.initials: X
authors.lastname: Krasnopolskaja
authors.forename: M L
authors.initials: ML
authors.lastname: Bondeson
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002675:Child, Preschool; D007446:Chromosome Inversion; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D020440:Gene Duplication; D015321:Gene Rearrangement; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics*; D007438:Introns; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016532:Mucopolysaccharidosis II / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D004247:DNA; D007066:Iduronate Sulfatase