Ring chromosome

About: Ring chromosome is a research topic. Over the lifetime, 1546 publications have been published within this topic receiving 31061 citations. The topic is also known as: supernumerary circular chromosome.

Ring chromosome 15 involving deletion of the insulin-like growth factor 1 receptor gene in a patient with features of Silver-Russell syndrome

Abstract: An 11-year-old girl with de novo r(15) (p12q26.3) with a clinical diagnosis of Silver-Russell syndrome (SRS) is presented. She had prenatal and postnatal growth deficiency with a severe short stature, peculiar facies characterized by a triangular face, a pinched nose with anteverted nostrils and down-turned corners of the mouth, bilateral clinodactyly of the fifth fingers, cafe-au-lait nevi, mental retardation, and a high level of serum follicular stimulating hormone. Southern blot analysis and chromosome fluorescence in situ hybridization revealed a deletion of the insulin-like growth factor 1 receptor gene (IGF1R) in the patient, the result indicating that IGF1R is assigned to 15q26.3. The deleted segment in our patient and comparisons with those of other reported cases of 15q-suggest that one of the putative SRS loci is at 15q26.3.

Asymmetry and skin pigmentary anomalies in chromosome mosaicism.

Abstract: We report six persons mosaic for a chromosome anomaly All were mentally retarded and dysmorphic Unilateral or asymmetrical features were found in all cases, in one an unusual transverse terminal limb anomaly, and in the others various degrees of hemiatrophy of the left side of the body Five of the subjects had skin pigmentary anomalies which were distributed in the lines of Blaschko The abnormal cell lines found were ring chromosome 22, trisomy 22, a large acrocentric marker, a deletion of 18q, a deletion of 8q, and triploidy In four cases the clinical diagnosis was only confirmed by skin biopsy In one case low level mosaicism in blood was fortuitously detected because of cytogenetic fragile X screening and confirmed in a skin biopsy The sixth case was of dynamic mosaicism of a non-mosaic deletion 18q with a chromosome 18 derived marker present in a proportion of cells Chromosome mosaicisn may cause subtle and asymmetrical clinical features and can require repeated cytogenetic investigations The diagnosis should be actively sought as it enables accurate genetic counselling to be given

Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

Abstract: Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of 'chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.