Prenatal diagnosis using combined quantitative fluorescent polymerase chain reaction and array comparative genomic hybridization analysis as a first‐line test: results from over 1000 consecutive cases

Scott, Fergus; Murphy, Kristi; Carey, Louise; Greville, W.D.; Mansfield, Nerida; Barahona, Paulette; Robertson, Rob; McLennan, Andrew

doi:10.1002/uog.12429

Cited by 55 publications

(59 citation statements)

References 26 publications

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“…While pregnancies found to have increased NT/nuchal fold or cystic hygroma had the highest rate of aneuploidy (30.9%), we did not detect any microdeletions or microduplications in this group. Some reports suggest that this ultrasound abnormality is not associated with an increased risk for submicroscopic chromosome abnormalities [30,[32][33][34] , but other studies have found such abnormalities using microarrays or other molecular tests, including the identification of some of the syndromes on our panel, such as 22q11.21 microdeletions [29,[35][36][37] .…”

Section: Discussionmentioning

confidence: 79%

Experience Using a Rapid Assay for Aneuploidy and Microdeletion/Microduplication Detection in over 2,900 Prenatal Specimens

Sa²,

Hummel³

et al. 2014

Fetal Diagn Ther

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Background: While microarray testing can identify chromosomal abnormalities missed by karyotyping, its prenatal use is often avoided in low-risk pregnancies due to the possible identification of variants of uncertain significance (VOUS). Methods: We tested 2,970 prenatal samples of all referral indications using a rapid BACs-on-Beads-based assay with probes for sex chromosomes, common autosomal aneuploidies, and 20 microdeletion/microduplication syndromes, designed as an alternative to microarray in low-risk pregnancies and an alternative to rapid aneuploidy testing in pregnancies also undergoing microarray analysis. Results: Interpretable results were obtained in 2,940 cases (99.0%), with 89% receiving results in 1 day. Aneuploidies were detected in 7.3% and partial chromosome abnormalities in 0.45% (n = 13), including 5 referred for maternal age, abnormal maternal serum screen, or isolated ultrasound markers. The added detection above karyotype was 1 in 745 in lower-risk cases with normal ultrasounds or isolated ultrasound markers/increased nuchal measurements and 1 in 165 for fetuses with structural/growth abnormalities. Neither false negatives nor false positives were found within test limitations. Female polyploidy could not be detected, while polyploidies with Y chromosomes were suspected and confirmed through additional analysis. Conclusion: When combined with karyotyping, this assay provides increased interrogation of specific chromosomal regions, while limiting VOUS identification.

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Section: Discussionmentioning

confidence: 79%

Experience Using a Rapid Assay for Aneuploidy and Microdeletion/Microduplication Detection in over 2,900 Prenatal Specimens

Sa²,

Hummel³

et al. 2014

Fetal Diagn Ther

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“…12 The results suggest that fetal anomalies on ultrasonography would be expected to be rare, consistent with the low prevalence of 15q13.3 deletions detected by prenatal chromosomal microarray studies. 11,23,24 Postnatal chromosomal microarray detection, perhaps secondary to referral for DD/ID, is higher. 9 By contrast, the most common large rare CNVs, 22q11.2 deletions, have high penetrance for both neuropsychiatric disorders and congenital anomalies, 25 and higher prenatal detection (0.29%) as compared with 15q13.3 deletions (0.02-0.09%).…”

Section: 5 Discussionmentioning

confidence: 99%

Delineating the 15q13.3 microdeletion phenotype: a case series and comprehensive review of the literature

Lowther

Costain

Stavropoulos

et al. 2015

Genetics in Medicine

115

145

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“…An increase in the prevalence of SL in affected pregnancies can also be observed in the data presented by Wapner et al (3.6 versus 0.8%) and by Scott et al (1.4 versus 0.55%). 7,37 If the phenotype of the SL involves a structural abnormality such as a heart anomaly in case of 1q21.1 duplication, an ultrasound investigation should be offered when the SL is encountered or when there is a family history of such a SL. Because of the higher prevalence of SL in fetuses with ultrasound abnormalities, it may seem to be defendable to offer a detailed second trimester ultrasound examination in all cases of SL or in families known to carry a SL.…”

Section: Rarity Of Particular Imbalances and Postnatal Biasmentioning

confidence: 99%

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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Prenatal diagnosis using combined quantitative fluorescent polymerase chain reaction and array comparative genomic hybridization analysis as a first‐line test: results from over 1000 consecutive cases

Abstract: Objectives First, to assess the performance of a prenatal diagnostic service using quantitative fluorescent polymerase chain reaction (QF-PCR)

Cited by 55 publications

References 26 publications

Experience Using a Rapid Assay for Aneuploidy and Microdeletion/Microduplication Detection in over 2,900 Prenatal Specimens

Experience Using a Rapid Assay for Aneuploidy and Microdeletion/Microduplication Detection in over 2,900 Prenatal Specimens

Delineating the 15q13.3 microdeletion phenotype: a case series and comprehensive review of the literature

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

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