Application of SNP array for rapid prenatal diagnosis: implementation, genetic counselling and diagnostic flow

Srebniak, Malgorzata I.; Boter, Marjan; Oudesluijs, Grétel; Joosten, Marieke; Govaerts, L.; Opstal, Diane Van; Galjaard, Robert-Jan H

doi:10.1038/ejhg.2011.119

Cited by 103 publications

(112 citation statements)

References 23 publications

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“…The cohort presented here includes cases published in our previous publications. 6,16 Since September 2012, SNP array testing is performed as a stand-alone first-tier test and therefore in only about 60 initial cases karyotyping was performed simultaneously to array. In some abnormal cases karyotyping was performed after array detected a pathogenic CNV to characterize the chromosome aberration and provide the risk for recurrence.…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

“…16 Since most of abnormalities found explained the fetal phenotype, and since there were no late-onset diseases found unexpectedly and we did not routinely release variants of unknown significance (VOUS), we realized that the extensive pre-test counseling system did not match the reality. We decided to simplify the pre-test counseling and stopped offering choices.…”

Section: Pre-test Counselingmentioning

confidence: 99%

“…A total of 50-100 ng fetal DNA was tested with~300 K Illumina HumanCytoSNP-12 (HCS) array (San Diego, CA, USA), as described before. 6,16 The array profiles were analyzed with a 0.15 Mb resolution in UCSC (Human Mar. 2006 (NCBI36/hg18) Assembly) by using initially Karyo Studio (Illumina), then Genome Studio (Illumina) and different versions of Nexus Copy Number (BioDiscovery: versions 5.0 and higher (Hawthorne, CA, USA)).…”

Section: Snp Array and Reportingmentioning

confidence: 99%

“…2006 (NCBI36/hg18) Assembly) by using initially Karyo Studio (Illumina), then Genome Studio (Illumina) and different versions of Nexus Copy Number (BioDiscovery: versions 5.0 and higher (Hawthorne, CA, USA)). 6,16 We did not use a filter, but in our experience events smaller that 150 kb most of the time occurred to be noisy and therefore we estimated the working resolution at 150 kb level. Fetal and parental DNA was simultaneously tested to determine the inheritance of CNVs, mainly to avoid subsequent testing, which delays the final reports.…”

Section: Snp Array and Reportingmentioning

confidence: 99%

“…Two pathogenic findings (2/1033, 0.2%) were detected exclusively thanks to B-allelic frequency (BAF) plot analysis, 16 which is 2.6% (2/76) of the pathogenic findings. These were the patients with a mosaic segmental uniparental isodisomy of 11p15 causing BeckwithWiedemann syndrome (Figure 1) and~10% mosaic trisomy 8 ( Figure 2).…”

Section: Pathogenic Array Findings In 1033 Fetusesmentioning

confidence: 99%

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Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

et al. 2015

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To evaluate the diagnostic value of single-nucleotide polymorphism (SNP) array testing in 1033 fetuses with ultrasound anomalies we investigated the prevalence and genetic nature of pathogenic findings. We reclassified all pathogenic findings into three categories: causative findings; unexpected diagnoses (UD); and susceptibility loci (SL) for neurodevelopmental disorders. After exclusion of trisomy 13, 18, 21, sex-chromosomal aneuploidy and triploidies, in 76/1033 (7.4%) fetuses a pathogenic chromosome abnormality was detected by genomic SNP array: in 19/1033 cases (1.8%) a microscopically detectable abnormality was found and in 57/1033 (5.5%) fetuses a pathogenic submicroscopic chromosome abnormality was detected. 58% (n = 44) of all these pathogenic chromosome abnormalities involved a causative finding, 35% (n = 27) a SL for neurodevelopmental disorder, and 6% (n = 5) a UD of an early-onset untreatable disease. In 0.3% of parental samples an incidental pathogenic finding was encountered. Our results confirm that a genomic array should be the preferred first-tier technique in fetuses with ultrasound anomalies. All UDs involved early-onset diseases, which is beneficial for the patients to know. It also seems that UDs occur at a comparable frequency among microscopic and submicroscopic pathogenic findings. SL were more often detected than in pregnancies without ultrasound anomalies.

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Section: Materials and Methods Materialsmentioning

confidence: 99%

Section: Pre-test Counselingmentioning

confidence: 99%

Section: Snp Array and Reportingmentioning

confidence: 99%

Section: Snp Array and Reportingmentioning

confidence: 99%

Section: Pathogenic Array Findings In 1033 Fetusesmentioning

confidence: 99%

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Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

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Management of Incidental Findings in Clinical Genomic Sequencing Studies

Dheensa

Shkedi‐Rafid

Crawford

et al. 2016

Encyclopedia of Life Sciences

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Whole‐genome approaches, which are replacing targeted tests in research and clinical practice, increase the chances of ‘incidental findings’ (IFs) – that is, those unrelated to the reason for the test. IFs raise several challenging questions, such as are researchers obliged to disclose IFs, and does this change if the researcher is also a clinician? How can the clinical significance of IFs be determined, and what significance level should determine disclosure? Could family members be tested to help to clarify significance, and if so, how? What should happen if adult‐onset risks are found in children or prenatally? No consensus currently exists about disclosing IFs from research, or about how participants can be helped to make decisions about and give consent (not) to receive them. We recommend that as more research studies that use genome‐wide tests are launched, longitudinal empirical work be conducted to explore participants' experiences and inform best practice for consent and, where relevant, feedback. Key Concepts Using genome‐wide tests increases the likelihood that findings outside the target area will be made. These are often called ‘incidental findings’ (IFs). Early empirical data show that the chances of finding IFs range between 1% and 7%, depending on the test used. IFs in genetic and genomic medicine differ from those found in imaging or biochemistry because they can predict future risks and risks to family members. Researchers generally are not thought to have a duty of care to research participants, but some experts argue that they ought to return IFs that are clinically valid, medically important and actionable, or even ‘hunt’ for additional findings that fit these criteria. However, research funding for such individualised approaches is often insufficient: protocols do not always include quality assurance procedures, and research teams lack health professionals who can communicate findings to participants. The research‐clinical practice boundary is often blurry: participation to some research studies is offered to patients in the clinic and some promise clinical feedback (e.g. the United Kingdom's 100 000 Genomes Project). Clinical validity is difficult to determine in both research and clinical practice, and this will not necessarily become easier with time, meaning upon discovery, IFs are better thought of as ‘potential incidental findings’. Paediatric IFs introduce more complexity: guidelines and legislation suggest that testing children for adult‐onset conditions should be deferred, but with IFs, the question is not about whether to test the child, but whether to reveal information already found. Prenatal IFs raise the additional issue that women might terminate pregnancies based on information that has uncertain significance. Research about participants' preferences shows that people want to know about all IFs, but this research has been hypothetical and cross‐sectional; thus, satisfaction with real‐life decisions has not been explored. The problem of hypothetical decision making is also relevant in real‐life research settings: at the time of consent, participants are unlikely to have thought about their choices or their implications. Empirical research is thus required to determine best practice in consent and disclosure.

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Prenatal Diagnosis by Microarray Analysis

Vermeesch¹

2015

Genetic Disorders and the Fetus

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Application of SNP array for rapid prenatal diagnosis: implementation, genetic counselling and diagnostic flow

Cited by 103 publications

References 23 publications

Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

Management of Incidental Findings in Clinical Genomic Sequencing Studies

Prenatal Diagnosis by Microarray Analysis

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