Complex X chromosome rearrangement delineated by array comparative genome hybridization in a woman with premature ovarian insufficiency

Ochalski, Melanie E.; Engle, Natalie; Wakim, Alain; Ravnan, Britt J.; Hoffner, Lori; Rajkovic, Aleksandar; Surti, Urvashi

doi:10.1016/j.fertnstert.2011.03.082

Cited by 9 publications

(5 citation statements)

References 11 publications

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“…However, when single and multiple chromosome errors were analyzed together, as shown in Figure 1B, we found that chromosome errors could occur in any of the 23 pairs of chromosomes, but errors in chromosome 21 (11.3%) were the most frequent chromosome anomaly, followed by chromosomes 22 (10.8%), 16 (7.7%), 7 (6.2%), and 15 (5.7%). When we analyzed chromosomes 13, 18, 21, and XY, which are the most common chromosomes examined by FISH, we found that only 12.7% of the blastocysts had these chromosome errors, and the rate increased to 29.5% if 12 chromosomes were analyzed (8,9,13,14,15,16,17,18,21,22, and XY). However, if all chromosomes were examined with microarray, 56.6% of the blastocysts had chromosome errors (Table 1).…”

Section: Chromosomal Errors Occur In Any Chromosomementioning

confidence: 94%

“…In the present study, we initially examined the detailed chromosome abnormalities in human blastocysts from the patients undergoing IVF, and then we examined whether chromosomes were consistent between TE and ICM cells in the same embryos. In order to assure the accuracy in this study, we used two different array platforms: one is a bacterial artificial chromosomal (BAC)-based microarray CGH that has already been applied to human PGD services [11-17, 19, 20], and another is an oligonucleotide (oligo) NimbleGen microarray provided by Roche [21], which is a more sensitive and higher-resolution platform that has been used in some research fields [22,23].…”

Section: Introductionmentioning

confidence: 99%

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DNA Microarray Reveals That High Proportions of Human Blastocysts from Women of Advanced Maternal Age Are Aneuploid and Mosaic1

Liu

Wang

Sun

et al. 2012

Biology of Reproduction

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Trophectoderm (TE) biopsy and DNA microarray have become the new technologies for preimplantation genetic diagnosis in humans. In this study, we comprehensively examined aneuploid formation in human blastocysts produced in vitro with microarray and investigated the clinical outcome after transfer of euploid embryos. Biopsied cells from either TE or inner cell mass (ICM) were processed for microarray to examine the errors in 23 pairs of chromosomes and the consistency between TE and ICM. It was found that 56.6% of blastocysts were aneuploid. Further analysis indicated that 62.3% of aneuploid blastocysts had single and 37.7% had multiple chromosomal abnormalities. Chromosome errors could occur in any chromosome, but errors in chromosome 21 accounted for the most (11.3%) among the 23 pairs of chromosomes. Transfer of array-screened blastocysts produced high pregnancy (70.2%) and implantation (63.5%) rates. Microarray of TE and ICM cells in the same blastocysts revealed that high proportions of aneuploid blastocysts (69.2%) were mosaic, including aneuploid TE and euploid ICM, inconsistent anomalies between ICM and TE, or euploid TE cells and aneuploid ICM in the same blastocyst. These results indicate that high proportions of human blastocysts produced in vitro from women of advanced maternal age are aneuploid and mosaic. Errors can occur in any of the 23 pairs of chromosomes in human blastocysts. Biopsy from TE in blastocysts does not exactly predict the chromosomal information in ICM if the embryos are aneuploid. Some mosaic blastocysts have euploid ICM, which may indicate important differentiate mechanism(s) of human preimplantation embryos.

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Section: Chromosomal Errors Occur In Any Chromosomementioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

DNA Microarray Reveals That High Proportions of Human Blastocysts from Women of Advanced Maternal Age Are Aneuploid and Mosaic1

Liu

Wang

Sun

et al. 2012

Biology of Reproduction

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“…© 2017 S. Karger AG, Basel Complex chromosomal rearrangements are common in cancer genomes and can also appear in the germline [Liu et al, 2011;Kloosterman and Cuppen, 2013]. To date, germline complex rearrangements have been identified in a small number of individuals [Liu et al, 2011;Ochalski et al, 2011;Auger et al, 2013;Kloosterman and Cuppen, 2013;Plaisancié et al, 2014]. Of these, complex autosomal rearrangements were often associated with congenital malformations and mental retardation, which probably reflect dysfunction or dysregulation of multiple genes on the affected chromosome [Liu et al, 2011;Kloosterman and Cuppen, 2013;Plaisancié et al, 2014].…”

mentioning

confidence: 99%

“…Of these, complex autosomal rearrangements were often associated with congenital malformations and mental retardation, which probably reflect dysfunction or dysregulation of multiple genes on the affected chromosome [Liu et al, 2011;Kloosterman and Cuppen, 2013;Plaisancié et al, 2014]. In contrast, complex X-chromosomal rearrangements were detected primarily in women with nonsyndromic ovarian dysfunction and were occasionally associated with other clinical features such as short stature, muscular hypotonia, and an unmasked X-linked recessive disorder [Ochalski et al, 2011;Auger et al, 2013]. The lack of severe developmental defects in women with complex X-chromosomal rearrangements is consistent with prior observations that structurally abnormal X chromosomes, except for X;autosome translocations, frequently undergo selective X inactivation [Heard et al, 1997].…”

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confidence: 99%

Complex X-Chromosomal Rearrangements in Two Women with Ovarian Dysfunction: Implications of Chromothripsis/Chromoanasynthesis-Dependent and -Independent Origins of Complex Genomic Alterations

Suzuki

Shima²,

Toki

et al. 2016

Cytogenet Genome Res

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Our current understanding of the phenotypic consequences and the molecular basis of germline complex chromosomal rearrangements remains fragmentary. Here, we report the clinical and molecular characteristics of 2 women with germline complex X-chromosomal rearrangements. Patient 1 presented with nonsyndromic ovarian dysfunction and hyperthyroidism; patient 2 exhibited various Turner syndrome- associated symptoms including ovarian dysfunction, short stature, and autoimmune hypothyroidism. The genomic abnormalities of the patients were characterized by array-based comparative genomic hybridization, high-resolution karyotyping, microsatellite genotyping, X-inactivation analysis, and bisulfite sequencing. Patient 1 carried a rearrangement of unknown parental origin with a 46,X,der(X)(pter→ p22.1::p11.23→q24::q21.3→q24::p11.4→pter) karyotype, indicative of a catastrophic chromosomal reconstruction due to chromothripsis/chromoanasynthesis. Patient 2 had a paternally derived isochromosome with a 46,X,der(X)(pter→ p22.31::q22.1→q10::q10→q22.1::p22.31→pter) karyotype, which likely resulted from 2 independent, sequential events. Both patients showed completely skewed X inactivation. CpG sites at Xp22.3 were hypermethylated in patient 2. The results indicate that germline complex X-chromosomal rearrangements underlie nonsyndromic ovarian dysfunction and Turner syndrome. Disease-causative mechanisms of these rearrangements likely include aberrant DNA methylation, in addition to X-chromosomal mispairing and haploinsufficiency of genes escaping X inactivation. Notably, our data imply that germline complex X-chromosomal rearrangements are created through both chromothripsis/chromoanasynthesis-dependent and -independent processes.

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“…In contrast to the severe pathogenicity of most germline complex rearrangements in autosomes, rearrangements involving the X chromosome has been identified in women with ovarian dysfunction as the sole recognizable clinical feature . In addition, a complex X chromosomal rearrangement was identified in a girl with an unmasked recessive mutation in CSF2RA and short stature .…”

Section: Clinical Consequences Of Complex Genomic Rearrangements In Tmentioning

confidence: 99%

Catastrophic cellular events leading to complex chromosomal rearrangements in the germline

et al. 2017

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Although complex chromosomal rearrangements were thought to reflect the accumulation of DNA damage over time, recent studies have shown that such rearrangements frequently arise from 'all-at-once' catastrophic cellular events. These events, designated chromothripsis, chromoanasynthesis, and chromoanagenesis, were first documented in the cancer genome and subsequently observed in the germline. These events likely result from micronucleus-mediated chromosomal shattering and subsequent random reassembly of DNA fragments, although several other mechanisms have also been proposed. Typically, only one or a few chromosomes of paternal origin are affected per event. These events can produce intrachromosomal deletions, duplications, inversions, and translocations, as well as interchromosomal translocations. Germline complex rearrangements of autosomes often result in developmental delay and dysmorphic features, whereas X chromosomal rearrangements are usually associated with relatively mild clinical manifestations. The concept of these catastrophic events provides novel insights into the etiology of human genomic disorders. This review introduces the molecular characteristics and phenotypic outcomes of catastrophic cellular events in the germline.

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Complex X chromosome rearrangement delineated by array comparative genome hybridization in a woman with premature ovarian insufficiency

Cited by 9 publications

References 11 publications

DNA Microarray Reveals That High Proportions of Human Blastocysts from Women of Advanced Maternal Age Are Aneuploid and Mosaic1

DNA Microarray Reveals That High Proportions of Human Blastocysts from Women of Advanced Maternal Age Are Aneuploid and Mosaic1

Complex X-Chromosomal Rearrangements in Two Women with Ovarian Dysfunction: Implications of Chromothripsis/Chromoanasynthesis-Dependent and -Independent Origins of Complex Genomic Alterations

Catastrophic cellular events leading to complex chromosomal rearrangements in the germline

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