Analysis of chromosomal abnormalities by CGH-array in patients with dysmorphic and intellectual disability with normal karyotype

Pratte-Santos, Rodrigo; Ribeiro, Katyanne Heringer; Santos, Thainá Altoe; Cintra, Terezinha Sarquis

doi:10.1590/s1679-45082016ao3592

Cited by 10 publications

(10 citation statements)

References 15 publications

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“…Chromosomal alterations associated with a spectrum of multiple congenital anomalies are most frequently numerical and are identified in 0.3–1% of newborns [ 13 , 14 ]. Partial tetrasomy 9 is not yet a well recognizable clinical syndrome due to the limited number of postnatal cases described to date.…”

Section: Discussionmentioning

confidence: 99%

Mosaic Tetrasomy of 9p24.3q21.11 postnatally identified in an infant born with multiple congenital malformations: a case report

Pinto

Minasi

Steckelberg³

et al. 2018

BMC Pediatr

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BackgroundSupernumerary Marker Chromosomes consist in structurally abnormal chromosomes, considered as an extra chromosome in which around 70% occur as a de novo event and about 30% of the cases are mosaic. Tetrasomy 9p is a rare chromosomal abnormality described as the presence of a supernumerary isochromosome 9p. Clinical features of tetrasomy 9p include a variety of physical and developmental abnormalities.Case presentationHerein, we reported a postnatal case of a newborn who died in early infancy with multiple congenital malformations due to a mosaic de novo tetrasomy 9p detected by Chromosomal Microarray Analysis. Conventional cytogenetics analysis of the proband was 47,XY,+mar[45]/46,XY[5]. The parental karyotypes presented no visible numerical or structural alterations. Microarray Analysis of the proband revealed that the marker chromosome corresponded to a mosaic de novo gain at 9p24.3q21.11.ConclusionsChromosomal Microarray Analysis was helpful to identify the origin of the supernumerary marker chromosome and it was a powerful tool to carry out genetic diagnostic, guiding the medical diagnosis. Furthermore, the CMA allowed observing at the first time in Central Brazil the tetrasomy 9p and partial tetrasomy 9q in mosaic, encompassing a large duplicated region with several morbid genes, in an infant with multiple congenital malformations.

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Section: Discussionmentioning

confidence: 99%

Mosaic Tetrasomy of 9p24.3q21.11 postnatally identified in an infant born with multiple congenital malformations: a case report

Pinto

Minasi

Steckelberg³

et al. 2018

BMC Pediatr

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“…Our cases support the benefit of offering microarray analysis to patients with a more severe phenotype such as ID and developmental delay, dysmorphic features or multiple CM, and when the clinical picture does not point toward a specific target region of the genome. A high rate of detection of unbalanced rearrangements using microarray methodology has been observed in patients with these referral indications [ 32 ]. It should be noted that microarrays can only detect unbalanced genomic regions, while the chromosomal locations of the duplicated or deleted regions material cannot be defined.…”

Section: Discussionmentioning

confidence: 99%

Derivative chromosomes involving 5p large rearranged segments went unnoticed with the use of conventional cytogenetics

et al. 2018

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BackgroundIn countries where comparative genomic hybridization arrays (aCGH) and next generation sequencing are not widely available due to accessibility and economic constraints, conventional 400–500-band karyotyping is the first-line choice for the etiological diagnosis of patients with congenital malformations and intellectual disability. Conventional karyotype analysis can rule out chromosomal alterations greater than 10 Mb. However, some large structural abnormalities, such as derivative chromosomes, may go undetected when the analysis is performed at less than a 550-band resolution and the size and banding pattern of the interchanged segments are similar. Derivatives frequently originate from inter-chromosomal exchanges and sometimes are inherited from a parent who carries a reciprocal translocation.Case presentationWe present two cases with derivative chromosomes involving a 9.1 Mb 5p deletion/14.8 Mb 10p duplication in the first patient and a 19.9 Mb 5p deletion/ 18.5 Mb 9p duplication in the second patient. These long chromosomal imbalances were ascertained by aCGH but not by conventional cytogenetics. Both patients presented with a deletion of the Cri du chat syndrome region and a duplication of another genomic region. Each patient had a unique clinical picture, and although they presented some features of Cri du chat syndrome, the phenotype did not conclusively point towards this diagnosis, although a chromosomopathy was suspected.ConclusionsThese cases highlight the fundamental role of the clinical suspicion in guiding the approach for the etiological diagnosis of patients. Molecular cytogenetics techniques, such as aCGH, should be considered when the clinician suspects the presence of a chromosomal imbalance in spite of a normal karyotype.

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“…Since 2010, CMA is widely recognized and recommended as the first-tier cytogenomic diagnostic test for individuals with unexplained developmental delay/intellectual disability (DD/ ID), autism spectrum disorders (ASDs), or multiple congenital anomalies, increasing the diagnostic yield around 10-25% [16,[30][31][32]. DD and ID are defined as several significant delays in developmental areas, including cognitive, speech, social/personal, fine/gross motor, and daily activities.…”

Section: Application In the Diagnosis Of Human Diseasesmentioning

confidence: 99%

“…MCAs are defined as multiple major structural malformations that cannot be explained by an underlying syndrome or sequence. These disorders might have a genetic etiology involving the gains and losses of CNVs and loss of heterozygosity (LOH), and the clinical consequences of these rearrangements are commonly associated with location, size, and the gene content (Figures 2 and 3) [32][33][34].…”

Section: Application In the Diagnosis Of Human Diseasesmentioning

confidence: 99%

Cytogenomic Microarray Testing

Pinto¹,

Cruz²,

Costa³

et al. 2019

Cytogenetics - Past, Present and Further Perspectives

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Cytogenomic microarray testing allows the detection of submicroscopic genomic rearrangements, commonly denominated copy number variations (CNVs) that are implicated with many neurodevelopmental disorders, dysmorphic features, multiple congenital anomalies, hematological and solid tumors, and complex disorders and traits in both humans and animals. On the other hand, this approach is also widely used for the identification of structural variations that are applied as a biomarker in pharmacogenomics, agriculture, and animal selection and breeding. The chromosomal microarray analysis (CMA) has been applied for over a decade to screen for submicroscopic genomic gains and losses in DNA sample in both diagnostic and functional scenarios. Herein, we present an overview of the fundamental concepts of cytogenomics and its potential application in human genetic diagnosis, agrigenomics, mutagenesis, and pharmacogenomics.

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Analysis of chromosomal abnormalities by CGH-array in patients with dysmorphic and intellectual disability with normal karyotype

Cited by 10 publications

References 15 publications

Mosaic Tetrasomy of 9p24.3q21.11 postnatally identified in an infant born with multiple congenital malformations: a case report

Mosaic Tetrasomy of 9p24.3q21.11 postnatally identified in an infant born with multiple congenital malformations: a case report

Derivative chromosomes involving 5p large rearranged segments went unnoticed with the use of conventional cytogenetics

Cytogenomic Microarray Testing

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