Two classes of low-copy repeats comediate a new recurrent rearrangement consisting of duplication at 8p23.1 and triplication at 8p23.2

Giorda, Roberto; Ciccone, Roberto; Gimelli, Giorgio; Pramparo, Tiziano; Beri, Silvana; Bonaglia, María Clara; Giglio, Sabrina; Genuardi, Maurizio; Argente, Jesús; Rocchi, Mariano; Zuffardi, Orsetta

doi:10.1002/humu.20465

Cited by 40 publications

(38 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 Although our approach was not designed to detect all VIPR2-associated CNVs, our findings complement and extend Vacic et al's 9 and Levinson et al's 10 observations. NAHR between VIPR2-associated LCRs is probably responsible for some of the rearrangements described by Vacic et al 7 In the populations examined, 7q63 rearrangements are rare (0.18% in our cohort, including the odd C182/C190 couple) or extremely rare (0.03-0.05%) 9,10 in controls and still fairly rare (0.25-0.35%) 9,10 in schizophrenia patients, whereas according to our results VIPR2-associated inversions are present in B0.8% of normal subjects of Italian descent. The frequency of VIPR2-associated inversions should be assessed on large cohorts of subjects of different ethnic background.…”

Section: Discussionmentioning

confidence: 86%

“…12,13 We also documented rare NAHR-mediated rearrangements at a pair of small inverted LCRs close to the MYOM gene on 8p. 7 Most nonrecurrent inverted duplications/terminal deletions seem to be generated by NHEJ or intra-strand annealing (reviewed in Zuffardi et al 12 ).…”

Section: Discussionmentioning

confidence: 99%

“…Inverted LCRs also have a role in mediating the generation of recurrent inverted duplications/deletions, 5 nonrecurrent duplications/ triplications 6 and more complex rearrangements. 7 While performing the molecular characterization of a patient with a complex 7q36 inverted duplication/terminal deletion, we documented the involvement of inverted LCRs enclosing exons 1 and 2 of the vasoactive intestinal peptide receptor (VIPR2) gene in the genesis of the rearrangement. We also demonstrated that the same LCRs mediate the occurrence of rare duplications/triplications encompassing the whole VIPR2 gene, and of an inversion polymorphism, presumably disrupting VIPR2 expression, in almost 1% of Italian subjects.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements

2012

Self Cite

View full text Add to dashboard Cite

Submicroscopic structural variations, including deletions, duplications, inversions and more complex rearrangements, are widespread in normal human genomes. Inverted segmental duplications or highly identical low-copy repeat (LCR) sequences can mediate the formation of inversions and more complex structural rearrangements through non-allelic homologous recombination. In a patient with 7q36 inverted duplication/terminal deletion, we demonstrated the central role of a pair of short inverted LCRs in the vasoactive intestinal peptide receptor gene (VIPR2)-LCRs in generating the rearrangement. We also revealed a relatively common VIPR2-LCR-associated inversion polymorphism disrupting the gene in almost 1% of healthy subjects, and a small number of complex duplications/triplications. In genome-wide studies of several thousand patients, a significant association of rare microduplications with variable size, all involving VIPR2, with schizophrenia was recently described, suggesting that altered vasoactive intestinal peptide signaling is likely implicated in the pathogenesis of schizophrenia. Genetic testing for VIPR2-LCR-associated inversions should be performed on available cohorts of psychiatric patients to evaluate their potential pathogenic role.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements

2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…A new type of rearrangement consisting of the duplication of 8p23.1 and the triplication of 8p23.2 [dup trp(8p)], mediated by the combined effects of two unrelated low copy repeats (LCRs), was found in two patients affected by mental retardation and minor facial dysmorphisms (52). The first set of LCRs consisted of the two OR-REPs involved in the recurrent inv dup del (8p).…”

Section: Inverted Duplications/ Triplications and Interstitial Triplimentioning

confidence: 99%

Inverted duplications deletions: underdiagnosed rearrangements??

et al. 2009

View full text Add to dashboard Cite

Molecular techniques led to the discovery that several chromosome rearrangements interpreted as terminal duplications were in fact inverted duplications contiguous to terminal deletions. Inv dup del rearrangements originate through a symmetric dicentric chromosome that, after asymmetric breakage, generates an inv dup del and a deleted chromosome. In recurrent inverted duplications the dicentric chromosome is formed at meiosis through non‐allelic homologous recombination. In non‐recurrent inv dup del cases, dicentric intermediates are formed by non‐homologous end joining or intrastrand annealing. Some authors hypothesized that in these cases the dicentric may have been formed directly in the zygote. Healing of the broken dicentric chromosomes can occur not only in a telomerase‐dependent way but also through telomere capture and circularization thus creating translocated or ring inv dup del chromosomes. In all the cases reported up to now, the duplicated region was always longer than the deleted one, but we can safely assume that there is another group of rearrangements where the deleted region is longer than the duplicated portion. In general, in these cases, the cytogeneticist will suspect the presence of a deletion and confirm it by FISH with a subtelomeric probe, but he/she will almost certainly miss the duplication. It is likely that the conventional analysis techniques used until now have led to a substantial underestimate of the frequency of inv dup del rearrangements and that the widespread use of array‐CGH in routine analysis will allow a more realistic estimate. Obviously, the concomitant presence of deletion and duplication has important consequences in genotype/phenotype correlations.

show abstract

“…[2][3][4][5][6] These REPD-and/or REPP-related 8p genomic rearrangements include (1) the 8p23.1 deletion or duplication between REPD and REPP, [6][7][8][9] (2) the 8p23.1 paracentric inversion between REPD and REPP, 8,10 (3) the pericentric inversion (inv(8)(p23.1q22.1)) and recombinant chromosome 8 (rec (8)dup(8q)inv(8)(p23.1q22.1)), 11 (4) the 8p interstitial inverted duplication with associated terminal deletion (inv dup del(8p)), 5,6,8,10,[12][13][14][15][16][17][18][19][20][21][22][23][24] (5) the 8p translocations involving the 8p23.1, 25,26 and (6) different types of supernumerary chromosome 8 (SMC (8)) involving the breakpoints within 8p23.1. 4,27 In addition to these defined 8p genomic abnormalities, other pathogenic genomic changes have been identified, [28][29][30] whereas numerous genomic imbalances on 8p are still described as copy number variants (CNVs) of unknown clinical significance or CNVs without apparent clinical significance (benign CNVs) (http://projects.tcag.ca/variation).…”

Section: Introductionmentioning

confidence: 99%

Genomic profile of copy number variants on the short arm of human chromosome 8

Fiedler

Stegner

et al. 2010

Eur J Hum Genet

View full text Add to dashboard Cite

We evaluated 966 consecutive pediatric patients with various developmental disorders by high-resolution microarray-based comparative genomic hybridization and found 10 individuals with pathogenic copy number variants (CNVs) on the short arm of chromosome 8 (8p), representing approximately 1% of the patients analyzed. Two patients with 8p terminal deletion associated with interstitial inverted duplication (inv dup del(8p)) had different mechanisms leading to the formation of a dicentric intermediate during meiosis. Three probands carried an identical B5.0 Mb interstitial duplication of chromosome 8p23.1. Four possible hotspots within 8p were observed at nucleotide coordinates of B10. 45, 24.32-24.82, 32.19-32.77, and 38.94-39.72 Mb involving the formation of recurrent genomic rearrangements. Other CNVs with deletion-or duplicationspecific start or stop coordinates on the 8p provide useful information for exploring the basic mechanisms of complex structural rearrangements in the human genome.

show abstract

Two classes of low-copy repeats comediate a new recurrent rearrangement consisting of duplication at 8p23.1 and triplication at 8p23.2

Cited by 40 publications

References 40 publications

Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements

Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements

Inverted duplications deletions: underdiagnosed rearrangements??

Genomic profile of copy number variants on the short arm of human chromosome 8

Contact Info

Product

Resources

About