Characterization of a de novo complex chromosomal rearrangement in a patient with cri‐du‐chat and trisomy 5p syndromes

Vera-Carbonell, Ascensión; Bafalliu, Juan Antonio; Guillén-Navarro, Encarna; Escalona, A.; Ballesta-Martínez, Maria Juliana; Fuster, Carme; Fernández, Asunción; López-Expósito, Isabel

doi:10.1002/ajmg.a.33055

Cited by 10 publications

(12 citation statements)

References 33 publications

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“…The exact breakpoints of the terminal deletions and interstitial duplications in these inv dup del(5p) vary, indicating that initial pre-meiotic doublestrand breaks of the 2 sister chromatids must occur randomly ( table 3 ). In contrast to all previously reported inv dup del(5p) where telomere healing was thought to repair the deleted terminal end of 5p [Kleczkowska et al, 1987;Sreekantaiah et al, 1999;Vetro et al, 2008;Wang et al, 2008;Rowe et al, 2009;Vera-Carbonell et al, 2009], the deleted terminal end of the inv dup del(5p) in patient 1 in this study was healed by an addition of the 13.17-Mb 5q terminus through a telomere capture mechanism ( fig. 1 ).…”

Section: Discussioncontrasting

confidence: 99%

“…Rarely observed inv dup del(5p), including the case reported in this study, are associated with U-type exchange mechanism (mechanism 3) for the formation of an intermediate symmetric dicentric chromosome in the prophase of meiosis I [Kleczkowska et al, 1987;Sreekantaiah et al, 1999;Vetro et al, 2008;Wang et al, 2008;Rowe et al, 2009;Vera-Carbonell et al, 2009]. Comparison of cases reported in this study with published literature is summarized in table 3 .…”

Section: Discussionsupporting

confidence: 54%

“…1 Kondoh et al, 2003;Beaujard et al, 2005;Daniel et al, 2008;Paskulin et al, 20094q Van Buggenhout et al, 20045p Kleczkowska et al, 1987Sreekantaiah et al, 1999;Wang et al, 2008;Rowe et al, 2009;Vera-Carbonell et al, 20097q Hoo et al, 1995Stetten et al, 19978p Dill et al, 1987Floridia et al, 1996;Giglio et al, 2001;Shimokawa et al, 20049p Teebi et al, 1993Mosca et …”

Section: Acgh Findingsmentioning

confidence: 99%

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Telomere Capture as a Frequent Mechanism for Stabilization of the Terminal Chromosomal Deletion Associated with Inverted Duplication

Graf²

2010

Cytogenet Genome Res

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We report 4 interstitial inverted duplications with associated terminal deletions (inv dup del) involving the short arms of chromosomes 5 and 8, and the long arm of chromosome 13 by microarray-based comparative genomic hybridization (aCGH) combined with chromosome banding (GTG banding) and fluorescence in situ hybridization (FISH) analyses. Formation of the intermediate dicentric chromosomes in 3 of them occurred through breakage-fusion-bridge cycle mechanism (U-type exchange mechanism) and in the fourth one it occurred through the mediation of the inverted low-copy repeats on chromosome 8p23.1. Two of these 4 inv dup del were confirmed and a third one was suspected to be associated with telomere capture for the healing of the terminal deletions. These findings indicate that a telomere capture mechanism is frequently used for stabilizing the broken chromosome ends in this type of genomic rearrangements. In addition, the inv dup del(13) represents the first observation of inv dup del on chromosome 13 in humans, the inv dup del(5) represents the first observation of inv dup del(5p) with an associated telomere capture, and unique features of the remaining two inv dup del(8p) were also discussed.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 54%

Section: Acgh Findingsmentioning

confidence: 99%

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Telomere Capture as a Frequent Mechanism for Stabilization of the Terminal Chromosomal Deletion Associated with Inverted Duplication

Graf²

2010

Cytogenet Genome Res

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“…Vetro et al [14] presented a prenatal case with cystic hygroma and other congenital facial and body anomalies, including dolichocephalia, low-set ears with malformed helices, microretrognathia and others. A newborn with similar chromosomal rearrangements of 5p was described by Vera-Carbonell et al [15], presenting both features of CdC syndrome and Trisomy 5p. The patient died at the age of three months due to a congenital heart defect.…”

Section: Discussionmentioning

confidence: 54%

A coalescence of two syndromes in a girl with terminal deletion and inverted duplication of chromosome 5

et al. 2014

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BackgroundRearrangements involving chromosome 5p often result in two syndromes, Cri-du-chat (CdC) and Trisomy 5p, caused by a deletion and duplication, respectively. The 5p15.2 has been defined as a critical region for CdC syndrome; however, genotype-phenotype studies allowed isolation of particular characteristics such as speech delay, cat-like cry and mental retardation, caused by distinct deletions of 5p. A varied clinical outcome was also observed in patients with Trisomy 5p. Duplications of 5p10-5p13.1 manifest themselves in a more severe phenotype, while trisomy of regions distal to 5p13 mainly causes mild and indistinct features. Combinations of a terminal deletion and inverted duplication of 5p are infrequent in literature. Consequences of these chromosomal rearrangements differ, depending on size of deletion and duplication in particular cases, although authors mainly describe the deletion as the cause of the observed clinical picture.Case presentationHere we present a 5-month-old Slovenian girl, with de novo terminal deletion and inverted duplication of chromosome 5p. Our patient presents features of both CdC and Trisomy 5. The most prominent features observed in our patient are a cat-like cry and severe malformations of the right ear.ConclusionThe cat-like cry, characteristic of CdC syndrome, is noted in our patient despite the fact that the deletion is not fully consistent with previously defined cat-like cry critical region in this syndrome. Features like dolichocephaly, macrocephaly and ear malformations, associated with duplication of the critical region of Trisomy 5p, are also present, although this region has not been rearranged in our case. Therefore, the true meaning of the described chromosomal rearrangements is discussed.

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“…Less than 5% of the patients have de novo translocations or other rare chromosomal aberrations such as complex chromosomal rearrangements (CCRs) [8], [9]. About 10%–15% of the 5p deletions result from unbalanced segregation of a parental balanced rearrangement such as translocation or inversion [10], but very rarely from a balanced parental insertion [11] or CCRs [12].…”

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

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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.

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Characterization of a de novo complex chromosomal rearrangement in a patient with cri‐du‐chat and trisomy 5p syndromes

Cited by 10 publications

References 33 publications

Telomere Capture as a Frequent Mechanism for Stabilization of the Terminal Chromosomal Deletion Associated with Inverted Duplication

Telomere Capture as a Frequent Mechanism for Stabilization of the Terminal Chromosomal Deletion Associated with Inverted Duplication

A coalescence of two syndromes in a girl with terminal deletion and inverted duplication of chromosome 5

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

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