title: Chromosome therapy. Correction of large chromosomal aberrations by inducing ring chromosomes in induced pluripotent stem cells (iPSCs).
abstract: The fusion of the short (p) and long (q) arms of a chromosome is referred to as a "ring chromosome." Ring chromosome disorders occur in approximately 1 in 50,000-100,000 patients. Ring chromosomes can result in birth defects, mental disabilities, and growth retardation if additional genes are deleted during the formation of the ring. Due to the severity of these large-scale aberrations affecting multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have so far been proposed. Our recent study (Bershteyn et al.) using patient-derived fibroblast lines containing ring chromosomes, found that cellular reprogramming of these fibroblasts into induced pluripotent stem cells (iPSCs) resulted in the cell-autonomous correction of the ring chromosomal aberration via compensatory uniparental disomy (UPD). These observations have important implications for studying the mechanism of chromosomal number control and may lead to the development of effective therapies for other, more common, chromosomal aberrations.
authors.affiliation: a Department of Genetics and Genome Sciences; School of Medicine; Case Western Reserve University School of Medicine; Cleveland, OH USA.
authors.forename: Taehyun
authors.initials: T
authors.lastname: Kim
authors.forename: Marina
authors.initials: M
authors.lastname: Bershteyn
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
mesh_terms: D064987:Cell- and Tissue-Based Therapy; D002869:Chromosome Aberrations; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000235:genetics* / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D012303:Ring Chromosomes; D024182:Uniparental Disomy / Q000235:genetics
keywords: Miller Dieker Syndrome (MDS); chromosome therapy; compensatory uniparental disomy (UPD); induced pluripotent stem cells (iPSCs); ring chromosomes