De novo dup p/del q or dup q/del p Rearranged Chromosomes: Review of 104 Cases of a Distinct Chromosomal Mutation

Rivera, Horacio; Domínguez, María G.; Vásquez-Velásquez, Ana I.; Lurie, Iosif W.

doi:10.1159/000351184

Cited by 10 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since there are two normal X chromosomes in the 15q duplication cell line, we assume that the unbalanced translocation involving two homologous chromosomes 15 was the first event. Similar chromosomal findings have been reported as a recombinant‐like chromosome, and arise in meiosis or are postzygotically mediated by non‐allelic homologous recombination (NAHR), nonhomologous end joining, or telomere transposition [Rivera et al, ]. The formation of the derivative chromosome X resulting in Xp deletion is either a secondary event from the further rearrangement of the derivative chromosome 15 for rescue purpose during mitosis, or may have occurred simultaneously as the derivative 15q in a different cell population; however, the lack of a normal cell line supports the 15q rescue mechanism.…”

Section: Discussionsupporting

confidence: 58%

Detection of mutually exclusive mosaicism in a girl with genotype‐phenotype discrepancies

Luo

Mulchandani

Dubbs

et al. 2015

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Discordance between clinical phenotype and genotype has multiple causes, including mosaicism. Phenotypes can be modified due to tissue distribution, or the presence of multiple abnormal cell lines with different genomic contributions. We have studied a 20-month-old female whose main phenotypes were failure to thrive, developmental delay, and patchy skin pigmentation. Initial chromosome and SNP microarray analysis of her blood revealed a non-mosaic ~24 Mb duplication of 15q25.1q26.3 resulting from the unbalanced translocation of terminal 15q to the short arm of chromosome 15. The most common feature associated with distal trisomy 15q is prenatal and postnatal overgrowth, which was not consistent with this patient’s phenotype. The phenotypic discordance, in combination with the patchy skin pigmentation, suggested the presence of mosaicism. Further analysis of skin biopsies from both hyper- and hypopigmented regions confirmed the presence of an additional cell line with the short arm of chromosome X deleted and replaced by the entire long arm of chromosome 15. The Xp deletion, consistent with a variant Turner Syndrome diagnosis, better explained the patient’s phenotype. Parental studies revealed that the alterations in both cell lines were de novo and the duplicated distal 15q and the deleted Xp were from different parental origins, suggesting a mitotic event. The possible mechanism for the occurrence of two mutually exclusive structural rearrangements with both involving the long arm of chromosome 15 is discussed.

show abstract

Section: Discussionsupporting

confidence: 58%

Detection of mutually exclusive mosaicism in a girl with genotype‐phenotype discrepancies

Luo

Mulchandani

Dubbs

et al. 2015

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Complex rearrangements involving a terminal short arm duplication and a terminal long arm deletion of the same chromosome may result from meiotic recombination of a parental pericentric inversion as in one patient reported by Armstrong et al, 2005 [6]. However many of these cases are the result of a de novo event [10], suggesting that the rearrangement may occur in two steps, the first resulting in a terminal deletion lately repaired by the capture of the telomere of the opposite arm, thus resulting in its duplication [9,11]. In our case both parents had a normal karyotype, suggesting that the rearrangement most likely occurred through this mechanism.…”

Section: Resultsmentioning

confidence: 99%

Severe growth hormone deficiency and pituitary malformation in a patient with chromosome 2p25 duplication and 2q37 deletion

Vetro

Pagani

Silengo³

et al. 2014

Mol Cytogenet

View full text Add to dashboard Cite

We report on a male child ascertained at 4.8 years of age with severe growth failure, growth hormone (GH) deficiency, psychomotor delay with prevalent speech impairment, and a distinct phenotype. An evaluation of his hypothalamic-pituitary region by Magnetic Resonance Imaging (MRI) revealed pituitary hypoplasia with pituitary stalk interruption and ectopic posterior pituitary lobe, which are considered prognostic markers of permanent GH deficiency. Prenatal chromosome analysis because of increased nuchal translucency revealed a normal male karyotype, whereas postnatal high resolution banding raised the suspicion of a 2q abnormality. Subsequently, array Comparative Genomic Hybridization (array-CGH) revealed a de novo complex genomic rearrangement consisting of a 2p25 duplication and a 2q37 deletion: arr[hg19] 2p25.3p25.1(30,341-9,588,369)x3,2q37.2q37.3(235,744,424-243,041,305)x1. FISH analysis showed that the abnormal chromosome 2 mimicked the derivative of an inversion with the duplicated 2p region located distally at 2q. This is, to the best of our knowledge, the first case with distal 2p25 duplication and 2q37 deletion and pituitary malformation leading to GH deficiency.

show abstract

“…Sometimes, the de novo unbalanced chromosome mimicks a recombinant from a parental pericentric inversion (Rivera et al 2013) in which the deleted arm ends with the distal portion of the opposite arm. The frequency of this type of translocation, to which we will refer as "de novo unbalanced inversion", is unknown.…”

Section: Introductionmentioning

confidence: 99%

De novo unbalanced translocations have a complex history/aetiology

et al. 2018

View full text Add to dashboard Cite

We investigated 52 cases of de novo unbalanced translocations, consisting in a terminally deleted or inverted-duplicated deleted (inv-dup del) 46th chromosome to which the distal portion of another chromosome or its opposite end was transposed. Array CGH, whole-genome sequencing, qPCR, FISH, and trio genotyping were applied. A biparental origin of the deletion and duplication was detected in 6 cases, whereas in 46, both imbalances have the same parental origin. Moreover, the duplicated region was of maternal origin in more than half of the cases, with 25% of them showing two maternal and one paternal haplotype. In all these cases, maternal age was increased. These findings indicate that the primary driver for the occurrence of the de novo unbalanced translocations is a maternal meiotic non-disjunction, followed by partial trisomy rescue of the supernumerary chromosome present in the trisomic zygote. In contrast, asymmetric breakage of a dicentric chromosome, originated either at the meiosis or postzygotically, in which the two resulting chromosomes, one being deleted and the other one inv-dup del, are repaired by telomere capture, appears at the basis of all inv-dup del translocations. Notably, this mechanism also fits with the origin of some simple translocations in which the duplicated region was of paternal origin. In all cases, the signature at the translocation junctions was that of non-homologous end joining (NHEJ) rather than nonallelic homologous recombination (NAHR). Our data imply that there is no risk of recurrence in the following pregnancies for any of the de novo unbalanced translocations we discuss here.

show abstract

De novo dup p/del q or dup q/del p Rearranged Chromosomes: Review of 104 Cases of a Distinct Chromosomal Mutation

Cited by 10 publications

References 20 publications

Detection of mutually exclusive mosaicism in a girl with genotype‐phenotype discrepancies

Detection of mutually exclusive mosaicism in a girl with genotype‐phenotype discrepancies

Severe growth hormone deficiency and pituitary malformation in a patient with chromosome 2p25 duplication and 2q37 deletion

De novo unbalanced translocations have a complex history/aetiology

Contact Info

Product

Resources

About