Noninvasive Prenatal Diagnosis of a Fetal Microdeletion Syndrome

Peters, David G.; Chu, Tianjiao; Yatsenko, Svetlana A.; Hendrix, Nancy W.; Hogge, W. Allen; Surti, Urvashi; Bunce, Kimberly; Dunkel, Mary K.; Shaw, Patricia; Rajkovic, Aleksandar

doi:10.1056/nejmc1106975

Cited by 121 publications

(110 citation statements)

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“…Expanding NIPS to include detection of specific conditions caused by a CNV (e.g., 22q11.2 deletion, 1p36 deletion, 15q11.2-13 deletion) is technically possible (analytical validity). [60][61][62][63] The phenotypes associated with these conditions can be severe; therefore, they may be appropriate conditions for prenatal screening. However, providers and patients must be aware that expanding the use of NIPS to include the detection of CNVs requires in-depth knowledge of the limitations of the technology, return of results, and follow-up.…”

Section: Acmg Statement Should Nips Be Offered For Detection Of Copy mentioning

confidence: 99%

“…Validation studies make the point that DR and SPEC depend on many variables (e.g., depth of read), 10,[60][61][62][63] which can change the false-positive and false-negative rate when NIPS is used for prenatal detection of CNVs. Pretest and posttest counseling is further confounded by variable expressivity and penetrance of the conditions being screened, size of the deletion being screened, specific genes within the critical region of the locus interrogated, and the number of genes within the critical region being screened.…”

Section: Acmg Statement Should Nips Be Offered For Detection Of Copy mentioning

confidence: 99%

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Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

Gregg

Skotko

Benkendorf

et al. 2016

Genetics in Medicine

564

551

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guidelines and statements have assisted patients seeking prenatal screening information and health-care providers responsible for providing accurate and up-to-date information to their patients. [1][2][3] Until recently, noninvasive prenatal screening for aneuploidy relied on measurements of maternal serum analytes and/or ultrasonography. These have a false-positive rate of approximately 5% and detection rates of 50-95%, depending on the specific screening strategy used. Advances in genomic technologies led to noninvasive prenatal screening that relies on the presence of cell-free DNA derived from the placenta but circulating in maternal blood, which is referred to here as noninvasive prenatal screening (NIPS). Massive parallel sequencing of maternal and placental (also called fetal when speaking of the fraction of this DNA in maternal blood) fragments of DNA occurs simultaneously. Sequencing with quantification can be random, targeted, and followed by quantification or exploitation of single-nucleotide polymorphisms. [4][5][6][7][8] Alternatively, sequencing can take place by measuring the release of hydrogen ions as nucleotides are added to a DNA template (i.e., semiconductor sequencing). 9 Microarray technology can also be used to quantify DNA. 10 Bioinformatics that enable these methodologies is complex and proprietary. Since the introduction of NIPS in 2011, health-care providers and patients have experienced marketing pressures, rapidly evolving professional practice guidelines, and confusion regarding the appropriate role of Noninvasive prenatal screening using cell-free DNA (NIPS) has been rapidly integrated into prenatal care since the initial American College of Medical Genetics and Genomics (ACMG) statement in 2013. New evidence strongly suggests that NIPS can replace conventional screening for Patau, Edwards, and Down syndromes across the maternal age spectrum, for a continuum of gestational age beginning at 9-10 weeks, and for patients who are not significantly obese. This statement sets forth a new framework for NIPS that is supported by information from validation and clinical utility studies. Pretest counseling for NIPS remains crucial; however, it needs to go beyond discussions of Patau, Edwards, and Down syndromes. The use of NIPS to include sex chromosome aneuploidy screening and screening for selected copy-number variants (CNVs) is becoming commonplace because there are no other screening options to identify these conditions. Providers should have a more thorough understanding of patient preferences and be able to educate about the current drawbacks of NIPS across the prenatal screening spectrum. Laboratories are encouraged to meet the needs of providers and their patients by delivering meaningful screening reports and to engage in education. With health-care-provider guidance, the patient should be able to make an educated decision about the current use of NIPS and the ramifications of a positive, negative, or no-call result. Genet Med advance online publication 28 July 2016Key Words: cell-f...

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Section: Acmg Statement Should Nips Be Offered For Detection Of Copy mentioning

confidence: 99%

Section: Acmg Statement Should Nips Be Offered For Detection Of Copy mentioning

confidence: 99%

Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics

Gregg

Skotko

Benkendorf

et al. 2016

Genetics in Medicine

564

551

View full text Add to dashboard Cite

show abstract

“…Prenatal cell‐free DNA (cfDNA) testing, or non‐invasive prenatal testing, has been shown to be capable of detecting certain microdeletion syndromes1 and has recently been extended to genome‐wide detection of subchromosomal abnormalities, including microduplications2. Here we describe a fetus with multiple structural anomalies that was diagnosed with double segmental duplications by cfDNA testing at our laboratory (Department of Genomic Medicine, Changhua Christian Hospital, Taiwan).…”

mentioning

confidence: 99%

“…FISH and CMA are the standard methods for genetic diagnosis6. With the development of massively parallel sequencing of cfDNA in maternal plasma, non‐invasive testing has been applied successfully to detect certain microdeletion syndromes1. However, it is still challenging to regularly detect microduplications as there is only a 1.5‐fold change in copy number (3:2) instead of a 2‐fold change (1:2) that occurs during microdeletions.…”

mentioning

confidence: 99%

Detection of 22q11.2 microduplication by cell‐free DNA screening and chromosomal microarray in fetus with multiple anomalies

Lin

et al. 2016

Ultrasound in Obstet & Gyne

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“…about noninvasive screening for submicroscopic chromosome aberrations associated with clinically significant disorders, 5 the reliability and accuracy of NIPT for detection of such conditions have not been subjected to the rigor necessary to make this a valid clinical test. We recommend that additional research studies be completed and results followed up in academic institutions with appropriate diagnostic testing before clinical noninvasive testing for segmental aneuploidies and microdeletions is offered in clinical practice.…”

mentioning

confidence: 99%