Inverted duplications: how many of them are mosaic?

Pramparo, Tiziano; Giglio, Sabrina; Gregato, Giuliana; Gregori, Manuela De; Patricelli, Maria Grazia; Ciccone, Roberto; Scappaticci, Susi; Mannino, Gaetano; Lombardi, Claudio; Pirola, Barbara; Giorda, Roberto; Rocchi, Mariano; Zuffardi, Orsetta

doi:10.1038/sj.ejhg.5201240

Cited by 32 publications

(34 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the finding that interphase FISH analysis with the subtelomeric probe (TEL8q Cytocell) (Figure 2a) showed two clearly separated signals suggests that a single copy region might be present distal to the duplicated one. Although we could not demonstrate the presence of the distal deletion associated to the duplication, we cannot exclude it and it seems likely that the original product of the abnormal maternal meiosis originating the rearrangement present in the proposita were a dicentric chromosome 8pter-8q24.3H8p24.3-8pter that, at meiosis II or during early embryogenesis, 26 underwent a breakage leading to the present inv dup(8)(q24.3) characterized by a very distal 8q deletion and a 2.3 Mb duplication.…”

Section: Discussionmentioning

confidence: 76%

A 2.3 Mb duplication of chromosome 8q24.3 associated with severe mental retardation and epilepsy detected by standard karyotype

et al. 2005

Self Cite

View full text Add to dashboard Cite

Chromosome duplications are found in about 2% of subjects with a typical chromosomal phenotype but their frequency is likely to be higher, as suggested by the first array-CGH data. According to the orientation of the duplicated segment, duplications may be in tandem or inverted. The latter are usually associated with a distal deletion. We studied a de novo 2.3 Mb inverted duplication of 8q24.3 without apparently associated deletion in a subject with profound psychomotor retardation, idiopathic epilepsy and growth delay. In spite of its small size, the presence of the rearrangement was suspected on standard karyotypes (approximately 400 bands) and later confirmed by Fluorescent in situ hybridization (FISH) analysis. We hypothesize that the GRINA gene, a glutamate binding subunit of NMDA receptor ion channel lying within the duplicated segment, may be responsible for the epilepsy. This paper confirms that small subtelomeric de novo duplications may be responsible for mental retardation, facial dysmorphisms and/or congenital malformations, although their presence may be overlooked by FISH analysis.

show abstract

Section: Discussionmentioning

confidence: 76%

A 2.3 Mb duplication of chromosome 8q24.3 associated with severe mental retardation and epilepsy detected by standard karyotype

et al. 2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…DNA extraction, labeling, hybridization and detection and FISH experiments were undertaken, as described previously. 9 We also performed analysis of the breakpoints with self-chain and segmental duplications repeats tools from UCSC Genome Bioinformatics (http://genome.ucsc.edu/).…”

Section: Methodsmentioning

confidence: 99%

Dysmorphic features, simplified gyral pattern and 7q11.23 duplication reciprocal to the Williams-Beuren deletion

et al. 2008

Self Cite

View full text Add to dashboard Cite

We report a patient with mild pachygyria, ascertained during a screening of subjects with abnormal neuronal migration and/or epilepsy, having a 7q11.23 duplication reciprocal to the Williams-Beuren critical region (WBCR) deletion. He exhibited speech delay and mental retardation together to type II trigonocephaly and other abnormalities. The proband's mother carried the same imbalance, though her phenotype was milder and no abnormal conformation of the cranium was reported. She had suffered a few seizures in infancy, as already described in other duplicated subjects. This genomic imbalance, now described in 17 subjects, including one parent for each of the four probands, is associated with a variable phenotype. Speech impairment is present in most cases; no distinctive facial gestalt is recognizable; seizures have been reported in four subjects and brain magnetic resonance, performed in eight cases, resulted abnormal in six, while detected abnormal neuronal migration in two. Although the clinical description of additional cases is needed to delineate a definite phenotypic core for WBCR duplications, trigonocephaly, also reported in another dup(7)(q11.23) patient, is possibly a trait that, together with speech impairment, may call for clinically oriented specific screening. Abnormal development of the cerebral cortex, reported also in the Williams-Beuren deletion, suggests that at least one gene is present in the critical region whose deletion/duplication impairs neuronal migration.

show abstract

“…The dicentric chromosome, in theory, can undergo breakage during meiosis or it can be inherited as such in the zygote. A few cases of mosaicism with different derivatives of the dicentric indeed suggest that the dicentric is usually present in the zygote: both Soler et al (11) and Pramparo et al (12) found in chorionic villi samples two cell lines, one with a del(8)(p11), the other one with an inv dup del(8p). In the case analyzed by Pramparo et al, a third cell line was also present with an inv dup del(8p) ending with the satellites of a D or a G short arm, suggesting that here the inv dup del(8p) had been stabilized through telomere capture leading to a translocated inv dup del chromosome.…”

Section: History Of a Recurrent Rearrangementmentioning

confidence: 96%

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

Inverted duplications: how many of them are mosaic?

Cited by 32 publications

References 29 publications

A 2.3 Mb duplication of chromosome 8q24.3 associated with severe mental retardation and epilepsy detected by standard karyotype

A 2.3 Mb duplication of chromosome 8q24.3 associated with severe mental retardation and epilepsy detected by standard karyotype

Dysmorphic features, simplified gyral pattern and 7q11.23 duplication reciprocal to the Williams-Beuren deletion

Inverted duplications deletions: underdiagnosed rearrangements??

Contact Info

Product

Resources

About