title: The constitutional t(17;22): another translocation mediated by palindromic AT-rich repeats.
abstract: We have demonstrated that the breakpoints of the constitutional t(11;22) are located at palindromic AT-rich repeats (PATRRs) on 11q23 and 22q11. As a mechanism for this recurrent translocation, we proposed that the PATRR forms a cruciform structure that induces the genomic instability leading to the rearrangement. A patient with neurofibromatosis type 1 (NF1) had previously been found to have a constitutional t(17;22) disrupting the NF1 gene on 17q11. We have localized the breakpoint on 22q11 within the 22q11-specific low-copy repeat where the breakpoints of the constitutional t(11;22)s reside, implying a similar palindrome-mediated mechanism for generation of the t(17;22). The NF1 gene contains a 195-bp PATRR within intron 31. We have isolated the junction fragments from both the der(17) and the der(22). The breakpoint on 17q11 is close to the center of the PATRR. A published breakpoint of an additional NF1-afflicted patient with a constitutional t(17;22) is also located close to the center of the same PATRR. Our data lend additional support to the hypothesis that PATRR-mediated genomic instability can lead to a variety of translocations.
authors.affiliation: Division of Human Genetics and Molecular Biology, the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Tamim
authors.initials: T
authors.lastname: Shaikh
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takata
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
mesh_terms: D001483:Base Sequence; D002503:Centromere / Q000235:genetics; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D002892:Chromosomes, Human, Pair 22; D018900:Dinucleotide Repeats / Q000235:genetics*; D005091:Exons; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008969:Molecular Sequence Data; D025542:Neurofibromin 1 / Q000235:genetics; D016615:Telomere / Q000235:genetics
chemical_list: D025542:Neurofibromin 1