title: Xp22.31 Microdeletion due to Microhomology-Mediated Break-Induced Replication in a Boy with Contiguous Gene Deletion Syndrome.
abstract: The Xp22.31 region is characterized by a low frequency of interspersed repeats and a low GC content. Submicroscopic deletions at Xp22.31 involving STS and ANOS1 (alias KAL1) underlie X-linked ichthyosis and Kallmann syndrome, respectively. Of the known microdeletions at Xp22.31, a common approximately 1.5-Mb deletion encompassing STS was ascribed to nonallelic homologous recombination, while 2 ANOS1-containing deletions were attributed to nonhomologous end-joining. However, the genomic bases of other microdeletions within the Xp22.31 region remain to be elucidated. Here, we identified a 2,735,696-bp deletion encompassing STS and ANOS1 in a boy with X-linked ichthyosis and Kallmann syndrome. The breakpoints of the deletion were located within Alu repeats and shared 2-bp microhomology. The fusion junction was not associated with nucleotide stretches, and the breakpoint-flanking regions harbored no palindromes or noncanonical DNA motifs. These results indicate that microhomology-mediated break-induced replication (MMBIR) can cause deletions at Xp22.31, resulting in contiguous gene deletion syndrome. It appears that interspersed repeats without other known rearrangement-inducing DNA features or high GC contents are sufficient to stimulate MMBIR at Xp22.31.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Nagai
authors.forename: Hirohito
authors.initials: H
authors.lastname: Shima
authors.forename: Miki
authors.initials: M
authors.lastname: Kamimura
authors.forename: Junko
authors.initials: J
authors.lastname: Kanno
authors.forename: Erina
authors.initials: E
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiguro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Narumi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Ikuma
authors.initials: I
authors.lastname: Fujiwara
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004261:DNA Replication; D016326:Extracellular Matrix Proteins / Q000235:genetics; D017353:Gene Deletion; D059765:Homologous Recombination; D006801:Humans; D007223:Infant; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D043266:Steryl-Sulfatase / Q000235:genetics; D013577:Syndrome
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C584039:STS protein, human; D043266:Steryl-Sulfatase