Prenatal diagnosis of a familial complex chromosomal rearrangement involving chromosomes 5, 10, 16 and 18

Lee, M. H.; Park, S. Y.; Kim, Y. M.; Kim, J. M.; Han, Jin‐Yeong; Kim, M. Y.; Ryu, Hyun-Mee

doi:10.1002/pd.224

Cited by 8 publications

(5 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When CCR is reevaluated by using advanced techniques, the number of breakpoints tends to increase over the number that initially was identified by using conventional cytogenetic techniques (22,23). The carriers of CCRs may transmit a balanced or unbalanced karyotype to offspring in the family (24)(25)(26). However, CCR carriers still have a limited chance of having a healthy child.…”

Section: Discussionmentioning

confidence: 97%

A healthy live birth after successful preimplantation genetic diagnosis for carriers of complex chromosome rearrangements

Lim

Cho

Kim

et al. 2008

Fertility and Sterility

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 97%

A healthy live birth after successful preimplantation genetic diagnosis for carriers of complex chromosome rearrangements

Lim

Cho

Kim

et al. 2008

Fertility and Sterility

View full text Add to dashboard Cite

“…These authors divided CCRs in 2 broad groups: one group ≤ 4 breaks and the other group >4 breaks. They observed that most familial CCRs belonged to the group with up to 4 breaks and have been transmitted by a balanced female carrier, whereas most of the de novo CCRs belonged to the group with more than 4 breaks and were of paternal origin [Kousseff et al, 1993;Batista et al, 1994;Joyce et al, 1999;Lee et al, 2002;Grasshoff et al, 2003;Kuechler et al, 2005]. The majority of the reported cases had 4 or less breaks [Pellestor et al, 2011].…”

Section: Definition and Classification Of Ccrsmentioning

confidence: 99%

Mechanisms of Origin, Phenotypic Effects and Diagnostic Implications of Complex Chromosome Rearrangements

Poot

Haaf

2015

Mol Syndromol

View full text Add to dashboard Cite

Complex chromosome rearrangements (CCRs) are currently defined as structural genome variations that involve more than 2 chromosome breaks and result in exchanges of chromosomal segments. They are thought to be extremely rare, but their detection rate is rising because of improvements in molecular cytogenetic technology. Their population frequency is also underestimated, since many CCRs may not elicit a phenotypic effect. CCRs may be the result of fork stalling and template switching, microhomology-mediated break-induced repair, breakage-fusion-bridge cycles, or chromothripsis. Patients with chromosomal instability syndromes show elevated rates of CCRs due to impaired DNA double-strand break responses during meiosis. Therefore, the putative functions of the proteins encoded by ATM, BLM, WRN, ATR, MRE11, NBS1, and RAD51 in preventing CCRs are discussed. CCRs may exert a pathogenic effect by either (1) gene dosage-dependent mechanisms, e.g. haploinsufficiency, (2) mechanisms based on disruption of the genomic architecture, such that genes, parts of genes or regulatory elements are truncated, fused or relocated and thus their interactions disturbed - these mechanisms will predominantly affect gene expression - or (3) mixed mutation mechanisms in which a CCR on one chromosome is combined with a different type of mutation on the other chromosome. Such inferred mechanisms of pathogenicity need corroboration by mRNA sequencing. Also, future studies with in vitro models, such as inducible pluripotent stem cells from patients with CCRs, and transgenic model organisms should substantiate current inferences regarding putative pathogenic effects of CCRs. The ramifications of the growing body of information on CCRs for clinical and experimental genetics and future treatment modalities are briefly illustrated with 2 cases, one of which suggests KDM4C(JMJD2C) as a novel candidate gene for mental retardation.

show abstract

“…are clinically utilized and have shown significant impact clinical human genetics, especially in diagnosing and counseling familial syndromes e.g. familial CCRs [21], [22] or familial 5p−/CDCs syndrome [23], [24].…”

Section: Introductionmentioning

confidence: 99%

A Familial Cri-du-Chat/5p Deletion Syndrome Resulted from Rare Maternal Complex Chromosomal Rearrangements (CCRs) and/or Possible Chromosome 5p Chromothripsis

Jiang

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

Cri-du-Chat syndrome (MIM 123450) is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs), diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5)(p13.3p15.33) spanning ∼26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5) (q23;p14.1p15.31),ins(21;5)(q21;p13.3p14.1),ins(21;5)(q21;p15.31p15.33),inv(7)(p22q32)dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5) identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5). Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family.

show abstract

Prenatal diagnosis of a familial complex chromosomal rearrangement involving chromosomes 5, 10, 16 and 18

Cited by 8 publications

References 9 publications

A healthy live birth after successful preimplantation genetic diagnosis for carriers of complex chromosome rearrangements

A healthy live birth after successful preimplantation genetic diagnosis for carriers of complex chromosome rearrangements

Mechanisms of Origin, Phenotypic Effects and Diagnostic Implications of Complex Chromosome Rearrangements

A Familial Cri-du-Chat/5p Deletion Syndrome Resulted from Rare Maternal Complex Chromosomal Rearrangements (CCRs) and/or Possible Chromosome 5p Chromothripsis

Contact Info

Product

Resources

About