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BMC Medical Genetics

, 12:171

Clinical-Molecular Genetics and Cytogenetics


BackgroundThe breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients.

MethodsSeveral techniques were performed such as genome-wide array, MLPA Multiplex Ligation-Dependent Probe Amplification and FISH Fluorescent in situ Hybridization.

ResultsThe ring chromosomes of patients I to XIV were determined to be, respectively: r3p26.1q29, r4p16.3q35.2, r10p15.3q26.2, r10p15.3q26.13, r13p13q31.1, r13p13q34, r14p13q32.33, r15p13q26.2, r18p11.32q22.2, r18p11.32q21.33, r18p11.21q23, r22p13q13.33, r22p13q13.2, and r22p13q13.2. These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion patients IV, VIII, IX, XI, XIII and XIV; a break in one chromosome arm followed by fusion with the subtelomeric region of the other patients I and II; a break in one chromosome arm followed by fusion with the opposite telomeric region patients III and X; fusion of two subtelomeric regions patient VII; and telomere-telomere fusion patient XII. Thus, the r14 and one r22 can be considered complete rings, since there was no loss of relevant genetic material. Two patients V and VI with r13 showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes II, XIII and XIV.

ConclusionsWe concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r14 and r22.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-12-171 contains supplementary material, which is available to authorized users.

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Autor: Roberta S Guilherme - Vera F Ayres Meloni - Chong A Kim - Renata Pellegrino - Sylvia S Takeno - Nancy B Spinner - Laura


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