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, Małgorzata; Tomaszewska, Agnieszka; Podbiol-Palenta, Agnieszka; Constantinou, Maria; Wawrzkiewicz-Witkowska, Angelika; Kowalski, Jeanne; Kałużewski, Bogdan; Zajączek, Stanisław; Srebniak, Malgorzata I.

doi:10.1159/000342165

Cited by 8 publications

(8 citation statements)

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“…Over the last decade recent advancement in molecular cytogenetic has proved to be an important tool for identification of complex chromosomal abnormalities including minor losses and gains with accurate breakpoint (27). The Copy number Variations (CNV's) are found to be associated with several disease conditions (28).…”

Section: Discussionmentioning

confidence: 99%

Partial trisomy 9 (9pter->9q22.1) and partial monosomy 14 (14pter>14q11.2) due to paternal translocation t(9;14)(q22.1;q11.2) in a case of Dysmorphic features

Dhangar

Korgaonkar

Vundinti

2019

IRDR

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Section: Discussionmentioning

confidence: 99%

Partial trisomy 9 (9pter->9q22.1) and partial monosomy 14 (14pter>14q11.2) due to paternal translocation t(9;14)(q22.1;q11.2) in a case of Dysmorphic features

Dhangar

Korgaonkar

Vundinti

2019

IRDR

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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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“…Indeed, several heterozygous chromosomal abnormalities were reported in patients with DWM, including aneuploidity (trisomy 21, 18 and 13), microdeletions (ie, 1q25.3–32.1, 3q22.3q24, 3q23q25, 3q24.3, 6p25 and 13q32.2-q33.2)8 9 and 9p duplication 10. Familial cases were reported 11 12.…”

Section: Introductionmentioning

confidence: 99%

Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood

et al. 2018

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BackgroundDandy-Walker malformation features agenesis/hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of posterior fossa. Although Dandy-Walker malformation is relatively common and several genes were linked to the syndrome, the genetic cause in the majority of cases is unknown.ObjectiveTo identify the mutated gene responsible for Dandy-Walker malformation, kidney disease and bone marrow failure in four patients from two unrelated families.MethodsMedical assessment, sonographic, MRI and pathological studies were used to define phenotype. Chromosomal microarray analysis and whole-exome sequence were performed to unravel the genotype.ResultsWe report four subjects from two unrelated families with homozygous mutations in the Exocyst Complex Component 3-Like-2 gene (EXOC3L2).EXOC3L2 functions in trafficking of post-Golgi vesicles to the plasma membrane. In the first family a missense mutation in a highly conserved amino acid, p.Leu41Gln, was found in three fetuses; all had severe forms of Dandy-Walker malformation that was detectable by prenatal ultrasonography and confirmed by autopsy. In the second family, the affected child carried a nonsense mutation, p.Arg72*, and no detected protein. He had peritrigonal and cerebellar white matter abnormalities with enlargement of the ventricular trigones, developmental delay, pituitary hypoplasia, severe renal dysplasia and bone marrow failure.ConclusionWe propose that biallelic EXOC3L2 mutations lead to a novel syndrome that affects hindbrain development, kidney and possibly the bone marrow.

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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

Cited by 8 publications

References 53 publications

Partial trisomy 9 (9pter->9q22.1) and partial monosomy 14 (14pter>14q11.2) due to paternal translocation t(9;14)(q22.1;q11.2) in a case of Dysmorphic features

Partial trisomy 9 (9pter->9q22.1) and partial monosomy 14 (14pter>14q11.2) due to paternal translocation t(9;14)(q22.1;q11.2) in a case of Dysmorphic features

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

Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood

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