Detection of mosaicism for genome imbalance in a cohort of 3,042 clinical cases using an oligonucleotide array CGH platform

Hoang, Sarah; Ahn, JooWook; Mann, Kathy; Bint, Sue; Mansour, Sahar; Homfray, Tessa; Mohammed, Shehla; Ogilvie, Caroline Mackie

doi:10.1016/j.ejmg.2010.10.010

Cited by 35 publications

(41 citation statements)

References 42 publications

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“…It is worth noting that this represents only 13 of 54 mosaic aberrations (24%) detected by SNP array, using both the LogR and BAF data, in this cohort of 5000 clinical samples (data not shown). The figure obtained here for low level mosaicism is not dissimilar to that obtained for all mosaic events detectable by aCGH 15 16 23. Previous aCGH ‘spiking experiments’ have determined with high accuracy the minimal detection of mosaicism to be 10% and 20% for whole chromosome and segmental abnormalities, respectively 14–16.…”

Section: Discussionsupporting

confidence: 51%

Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping

Bruno

White

Ganesamoorthy

et al. 2011

Journal of Medical Genetics

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These results demonstrate the utility of SNP genotyping data for detection of clinically significant abnormalities, including chimerism/mosaicism and recessive Mendelian disorders associated with autozygosity. The incidence of clinically significant low level mosaicism inferred from these cases suggests that this has hitherto been underestimated and chromosome mosaicism frequently occurs in the absence of indicative clinical features. The growing appreciation among clinicians and demand for SNP genotyping data poses significant challenges for the interpretation of LCSH, especially where there is no detailed phenotypic description to direct laboratory analysis. Finally, reporting of unexpected or hidden consanguinity revealed by SNP array analysis raises potential ethical and legal issues.

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Section: Discussionsupporting

confidence: 51%

Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping

Bruno

White

Ganesamoorthy

et al. 2011

Journal of Medical Genetics

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“…The third mosaic case, a small SMC, later identified as small NRC, was detected by conventional cytogenetics, but the precise identification of the material had been elusive until CMA analysis was performed. The incidence we observed is in line with what has been previously reported (0.2-1%) in patients with ID [Ballif et al, 2006;Cheung et al, 2007;Conlin et al, 2010;Bruno et al, 2011;Hoang et al, 2011]. Our findings underline the important role of low-level mosaics in the pathogenesis of NDDs of unknown etiology.…”

Section: Discussionsupporting

confidence: 81%

“…It is well-known that the standard analysis of 15 cells obtained by traditional cytogenetics only provides a diagnostic accuracy of ≥ 20% for mosaicism of an entire chromosome [Hook, 1977]. Detection limits of CMA have been determined at 5% for whole chromosomes and 20% for segmental mosaics [Ballif et al, 2006;Conlin et al, 2010;Scott et al, 2010;Hoang et al, 2011]. It has been suggested that for the detection of segmental low-level mosaics (<10%), CMA coupled with conventional chromosome studies on more than 15 cells should be performed [Bi et al, 2013].…”

confidence: 99%

Low-Level Chromosomal Mosaicism in Neurodevelopmental Disorders

et al. 2017

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Chromosomal mosaicism, which represents a diagnostic challenge for detection and interpretation, has been described in several genetic conditions. It can contribute to a large phenotypic variation in diseases. At analysis of a well-characterized cohort of 714 patients with neurodevelopmental disorders (NDDs) of unknown etiology using a high-resolution chromosomal microarray platform, we found 2 cases (0.28%) of low-level mosaicism and defined a previously detected extra chromosome in a third patient. Two of the cases were mosaics for segmental imbalances (a partial trisomy 3q26.1q27.3 and a partial monosomy 18q21.2qter with 14.6 and 20% mosaic ratios in lymphocytes, respectively), and 1 was a mosaic for an entire chromosome (trisomy 14, mosaic ratio 20%). Our diagnostic yield is in line with the ratios previously published in patients with intellectual disability. Notably, the partial trisomy 3q26.1q27.3 case is an example of a rare and unusual class of a rearranged neocentric ring chromosome, which can neither be categorized in class I, nor in class II of such rearrangements. Our cases further elucidate the phenotypes related to the aberrations of the specific chromosome segments observed and underline the important role of low-level mosaics in the pathogenesis of NDDs of unknown etiology even in the absence of clinical signs of mosaicism.

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“…6,13,14 Other array platforms, such as single-nucleotide polymorphism arrays may be better capable of detecting mosaicism by the information obtained from the B-allele frequencies. 15,16 Chromosome analysis can detect low-level mosaicism through the individual examination of large numbers of cells.…”

Section: Maximum Detection Of Mosaicism By a Conjunction Of Cma And Tmentioning

confidence: 99%

Comparison of chromosome analysis and chromosomal microarray analysis: what is the value of chromosome analysis in today’s genomic array era?

Borgan

Pursley

et al. 2013

Genetics in Medicine

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Detection of mosaicism for genome imbalance in a cohort of 3,042 clinical cases using an oligonucleotide array CGH platform

Cited by 35 publications

References 42 publications

Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping

Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping

Low-Level Chromosomal Mosaicism in Neurodevelopmental Disorders

Comparison of chromosome analysis and chromosomal microarray analysis: what is the value of chromosome analysis in today’s genomic array era?

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