Cytogenetic and Array-CGH Characterization of a Complex de novo Rearrangement Involving Duplication and Deletion of 9p and Clinical Findings in a 4-Month-Old Female

Hulick, Peter J.; Noonan, Kimberly; Kulkarni, Snehal; Donovan, Diana; Listewnik, Marc; Ihm, Chunhwa; Stoler, Joan M.; Weremowicz, Stanislawa

doi:10.1159/000251966

Cited by 25 publications

(29 citation statements)

References 63 publications

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“…However, results of Swinkels et al [2008] show that developmental features in children with 9p deletions are independent of the size of the deletion and they could not establish clear genotype-phenotype correlation for developmental aspects in the 9p deletion syndrome. Hulick et al [2009] reported the most similar case to the currently presented patient, but even here the duplication is about 4 Mb smaller than in our case and the deletion about 1 Mb larger. In contrast to our patient, their proband had cleft palate.…”

Section: Resultssupporting

confidence: 57%

“…Jelin et al [2010] suggested 2 candidate genes for clefting in 9p22: CER1 and FREM1 . Although both patients have duplication of both FREM1 and CER1, only the patient reported by Hulick et al [2009] has a cleft lip. It has already been shown that not all cases with duplications of 9p22p24 result in orofacial clefting [Jelin et al, 2010].…”

Section: Resultsmentioning

confidence: 91%

“…No precise breakpoints available. mined by use of high resolution array: the patients reported by Hulick et al [2009]: Agilent 244K array, Chen et al [2011]: Agilent 60K array and our case: Agilent 244K. In 2 cases the breakpoints were characterized by use of BAC arrays [Faas et al, 2007;Swinkels et al, 2008] and in all other cases the breakpoints are estimated based on cytogenetic and FISH results.…”

Section: Resultsmentioning

confidence: 97%

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Another Rare Case of a Child with de novo Terminal 9p Deletion and Co-Existing Interstitial 9p Duplication: Clinical Findings and Molecular Cytogenetic Study by Array-CGH

Kowalczyk

Tomaszewska²,

Podbiol-Palenta³

et al. 2012

Cytogenet Genome Res

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Trisomy 9p is the fourth most common chromosome abnormality found in liveborns. We report on a rare case of partial trisomy 9p complicated by partial monosomy 9p. Clinical manifestation included craniofacial abnormalities typical for trisomy 9p syndrome, developmental delay, mental retardation and brain anomaly in the form of Dandy-Walker malformation. The cytogenetic abnormality was investigated with FISH and array-CGH to characterize the breakpoints of the complex rearrangement. The patient’s karyotype was 46,XX,der(9)del(9)(p24)dup(9)(p21p24)dn.arr 9p24.3p24.2 (1–2,414,485)×1,9p24.2p21.3(2,414,485–24,101,280)×3. The cytogenetic rearrangement led to a 2.4-Mb deletion of 9p24.2pter and a 21.6-Mb duplication of 9p24.2p21.3. The clinical and cytogenetic findings in our and other similar patients are compared.

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Section: Resultssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 97%

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Another Rare Case of a Child with de novo Terminal 9p Deletion and Co-Existing Interstitial 9p Duplication: Clinical Findings and Molecular Cytogenetic Study by Array-CGH

Kowalczyk

Tomaszewska²,

Podbiol-Palenta³

et al. 2012

Cytogenet Genome Res

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“…Meanwhile, several authors described complex inversions and insertion-translocations, which, depending on the definition applied, may or may not have been labeled CCRs [Madan and Menko, 1992;Bernardini et al, 2008;Jiang et al, 2008;Lybaek et al, 2008;de Vree et al, 2009;Poot et al, 2009;Kang et al, 2010]. A special case of a CCR involving a single chromosome is the inversion-duplication-distal deletion rearrangement [Hulick et al, 2009;van Binsbergen et al, 2012;Kowalczyk et al, 2013;Trachoo et al, 2013]. These studies indicated that rearrangements involving only a single chromosome can also be 'complex'.…”

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

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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.

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“…3 and Table 2) (Al Achkar et al, 2010;Hulik et al, 2009;Swinkles et al, 2008). All show features shared by 9p deletion and 9p duplication syndromes, such as developmental delay, psychomotor retardation, hypotonia and low-set ears, but the manifestation of syndromespecific features is variable and depends on the length of the different genomic regions involved.…”

Section: Discussionmentioning

confidence: 99%

Complex rearrangement involving 9p deletion and duplication in a syndromic patient: Genotype/phenotype correlation and review of the literature

Recalcati

Bellini

Norsa

et al. 2012

Gene

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Keywords:Chromosome 9p complex rearrangement Array-CGH FISH 9p deletion syndrome 9p duplication syndrome Phenotype-genotype correlationWe describe a 7-year-old boy with a complex rearrangement involving the whole short arm of chromosome 9 defined by means of molecular cytogenetic techniques. The rearrangement is characterized by a 18.3 Mb terminal deletion associated with the inverted duplication of the adjacent 21,5 Mb region. The patient shows developmental delay, psychomotor retardation, hypotonia. Other typical features of 9p deletion (genital disorders, midface hypoplasia, long philtrum) and of the 9p duplication (brachycephaly, down slanting palpebral fissures and bulbous nasal tip) are present. Interestingly, he does not show trigonocephaly that is the most prominent dysmorphism associated with the deletion of the short arm of chromosome 9. Patient's phenotype and the underlying flanking opposite 9p imbalances are compared with that of reported patients and the proposed critical regions for 9p deletion and 9p duplication syndromes.

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Cytogenetic and Array-CGH Characterization of a Complex de novo Rearrangement Involving Duplication and Deletion of 9p and Clinical Findings in a 4-Month-Old Female

Cited by 25 publications

References 63 publications

Another Rare Case of a Child with de novo Terminal 9p Deletion and Co-Existing Interstitial 9p Duplication: Clinical Findings and Molecular Cytogenetic Study by Array-CGH

Another Rare Case of a Child with de novo Terminal 9p Deletion and Co-Existing Interstitial 9p Duplication: Clinical Findings and Molecular Cytogenetic Study by Array-CGH

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

Complex rearrangement involving 9p deletion and duplication in a syndromic patient: Genotype/phenotype correlation and review of the literature

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