Complex biology of constitutional ring chromosomes structure and (in)stability revealed by somatic cell reprogramming.

Human ring chromosomes are often unstable during mitosis, and daughter cells can be partially or completely aneuploid. We studied the mitotic stability of four ring chromosomes, 8, 13, 18, and 22, in long-term cultures of skin fibroblasts and induced pluripotent stem cells (iPSCs) by GTG karyotyping and aCGH. Ring chromosome loss and secondary aberrations were observed in all fibroblast cultures except for r(18).

Establishment of an induced pluripotent stem cell line (ICGi025-A) from fibroblasts of a patient with 46,XY,r(8)/45,XY,-8 mosaicism.

Ring chromosomes are structural aberrations commonly associated with disease phenotype. We consider necessary to create the iPSCs with a ring chromosome 8, which can be used for disease modeling and related research. The ICGi025-A iPSCs line was obtained by the reprogramming of the skin fibroblasts from a 1-year-old boy with 46,XY,r(8)/45,XY,-8 mosaicism, developmental delay, microcephaly, dysmorphic features, diffuse muscle hypotonia, moderate proximal muscle weakness, feeding problems, and motor alalia.

Induced pluripotent stem cell line, IMGTi003-A, derived from skin fibroblasts of an intellectually disabled patient with ring chromosome 13.

Skin fibroblasts from a patient with neurodevelopmental and speech delay, anxiety disorder, macrocephaly, microorchidism, multiple anomalies of internal organs and ring chromosome 13 were reprogrammed into induced pluripotent stem cells (iPSCs) to generate a clonal stem cell line IMGTi003-A (iTAF6-6). IMGTi003-A pluripotency was demonstrated by three germ layer differentiation capacity in vitro, and this cell line had a mosaic karyotype with 46,XY,r(13) as a predominant cell subpopulation. IMGTi003-A line is a good model for studying of the mitotic instability of the ring chromosome 13.

Generation of two iPSC lines (IMGTi001-A and IMGTi001-B) from human skin fibroblasts with ring chromosome 22.

Skin fibroblasts from a patient with intellectual disability and ring chromosome 22 were reprogrammed into induced pluripotent stem cells (iPSCs) to establish a clonal stem cell lines, IMGTi001-A (iTAF5-29) and IMGTi001-B (iTAF5-32). Because of ring chromosome mitotic instability these cell lines show mosaic karyotypes with 46,XX,r(22) in >83% cells, 45,XX,-22 as minor class and sporadically cells with other karyotypes. Differentiation in derivatives of all three germ layers was shown in teratoma assay for IMGTi001-A, and in embryoid bodies for both cell lines.

[Clinical and genetic analysis of idiopathic intellectual disability based on array comparative genomic hybridization].

In this study authors searched for chromosomal aberrations in 71 children with developmental delay or idiopathic mental retardation using Human Genome CGH Microarray Kits 4×44K and 8×60K (Agilent Technologies, USA). Microdeletions and microduplications, as well as CNV, which may be related to intellectual disability and associated with regions of known hereditary diseases or chromosomal syndromes were identified in 14 (20%) children (these patients are described in this article). During the analysis, candidate genes localized within the regions of aberrations and associated with development and functioning of nervous system were denoted.