Prenatal detection of Down's syndrome by rapid aneuploidy testing for chromosomes 13, 18, and 21 by FISH or PCR without a full karyotype: a cytogenetic risk assessment

Caine, A.; Maltby, A Edna; Parkin, C Anthony; Waters, Jonathan J.; Crolla, John A.

doi:10.1016/s0140-6736(05)66790-6

Cited by 111 publications

(100 citation statements)

References 19 publications

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“…This figure differs slightly from that predicted by Leung et al as we have not removed the uncertain or good prognosis group from our total abnormal karyotype group. A 2005 retrospective audit of >140 000 pregnancies by the Association of Clinical Cytogeneticists (Caine et al, 2005) found that QF-PCR for chromosomes 13, 18 and 21 detected approximately 70% of abnormal karyotypes (67% of abnormal AF and 78% of abnormal CV samples). The authors conclude that approximately 1 in 100 samples referred with a Down syndrome risk which received QF-PCR only would have an undetected autosomal chromosome abnormality and that 33% of these would have a substantial risk of serious phenotypic consequences.…”

Section: Discussionmentioning

confidence: 99%

“…Published audits of chromosome abnormalities found by karyotyping at prenatal diagnosis have consistently shown a prevalence of between 0.07% and 0.1% for clinically significant abnormalities that would not be detected by QF-PCR in samples from pregnancies without fetal ultrasound Copyright  2010 John Wiley & Sons, Ltd. abnormalities (Thein et al, 2000;Lewin et al, 2000;Ryall et al, 2001;Ogilvie et al, 2005), although a more cautiously interpreted audit concluded that approximately 1 in 100 samples referred with a Down syndrome risk which received QF-PCR only would have an undetected autosomal chromosome abnormality and that 33% of these would have a substantial risk of serious phenotypic consequences, equivalent to a prevalence of 0.33% (Caine et al, 2005). The anxiety, distress and potentially unnecessary pregnancy terminations that can follow equivocal karyotype results, plus the resource implications, especially for laboratories and counselling services, were put forward as an argument for replacing the traditional approach to prenatal diagnosis for women in this specific referral group.…”

Section: Introductionmentioning

confidence: 99%

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QF‐PCR as a stand‐alone test for prenatal samples: the first 2 years' experience in the London region

et al. 2010

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Objective To analyse the results of the first 2 years of a QF-PCR stand-alone testing strategy for the prenatal diagnosis of aneuploidy in the London region and to determine the advantages and disadvantages of this policy.Methods A review of the results of 9737 prenatal samples received for exclusion of chromosome abnormalities. All samples were subjected to QF-PCR testing for common aneuploidies but only samples fulfilling specific criteria subsequently had a full karyotype analysis. ResultsOf the 9737 samples received, 10.3% had a chromosome abnormality detected by QF-PCR testing. Of the 7284 samples received with no indication for karyotype analysis, 25 (0.3%) received a normal QF-PCR result but subsequently had an abnormal karyotype detected either prenatally as a privately funded test or postnatally. Of these samples, without subsequent abnormal ultrasound findings, five had a chromosome abnormality associated with a poor prognosis, representing 0.069% of samples referred for Down syndrome testing.Conclusion While back-up karyotyping is required for some samples, using QF-PCR as a stand-alone prenatal test for pregnancies without ultrasound abnormalities reduces costs, provides rapid delivery of results, and avoids ambiguous and uncertain karyotype results, reducing parental anxiety.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

QF‐PCR as a stand‐alone test for prenatal samples: the first 2 years' experience in the London region

et al. 2010

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“…As MLPA for prenatal diagnosis of common aneuploidies is now truly validated, the question raises whether MLPA can replace FISH and karyotyping for the most common indications. 25,26 For detection of the most common aneuploidies, FISH can be replaced by MLPA in most cases. MLPA is cheaper and less labor intensive compared with FISH, especially if more than five samples have to be processed.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of these undetected cases is about 0.4% by fetal karyotyping and an estimated 0.1% in live borns. 12,25,26 Currently, various studies show differences concerning the nature of chromosome aberrations considered to result in live born children with clinically significant abnormal phenotypes. 25 -28 In our opinion, it is important to define which chromosome anomalies can be considered to be clinically significant and to confirm given estimates (manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

Rapid aneuploidy detection with multiplex ligation-dependent probe amplification: a prospective study of 4000 amniotic fluid samples

et al. 2008

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The introduction of prenatal screening requires rapid high-throughput diagnosis of common aneuploidies. Multiplex ligation-dependent probe amplification (MLPA) allows for quick, easily automated multiplex testing of these aneuploidies in one polymerase chain reaction. We performed a large prospective study using MLPA on 4000 amniotic fluid (AF) samples including all indications and compared its value to karyotyping and fluorescence in situ hybridization (FISH). MLPA can reliably determine common aneuploidies with 100% sensitivity and 100% specificity. Moreover, some mosaic cases and structural chromosome aberrations were detected as well. In cases of a male fetus, triploidies can be detected by an aberrant pattern of probe signals, which mimics maternal cell contamination (MCC). Macroscopic blood contamination was encountered in 3.2% of the AF samples. In 20% of these samples, an MLPA pattern was found consistent with MCC, although there were no false negatives of the most common aneuploidies. As the vast majority of inconclusive results (1.7%) is due to potential MCC, we designed a protocol in which we determine whether MLPA can be performed on blood-contaminated AF samples by testing if blood is of fetal origin. Then, the number of inconclusive results could be theoretically reduced to 0.05%. We propose an alternative interpretation of relative probe signals for rapid aneuploidy diagnosis (RAD). We discuss the value of MLPA for the detection of (submicroscopic) structural chromosome anomalies. MLPA is a reliable method that can replace FISH and could be used as a stand-alone test for RAD instead of karyotyping.

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“…The women, who test positive by the screening programs, are offered RAD test as a standalone approach to rule out aneuploidies. In response to this decision by the NHS and NSC, Caine et al [8] from the Association of Clinical Cytogeneticists (ACC), conducted a large survey on 119,528 amniotic fluid and 23077 chorionic villus samples and showed that about 1 % of all prenatal samples would have a chromosomal abnormality which would go undetected by FISH and 33 % of these abnormalities would be of clinical importance. These 33 % abnormalities included the sex chromosomal and balanced translocations in their study.…”

Section: Discussionmentioning

confidence: 99%

FISH is not Suitable as a Standalone Test for Detecting Fetal Chromosomal Abnormalities

Lall

Mahajan

Saviour

et al. 2015

Journal of Fetal Medicine

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Karyotyping and fluorescence in situ hybridization (FISH) detect fetal chromosome abnormalities. The choice between karyotyping and FISH is still debatable. In a developing country, parents face an emotional and economic constraint of a prenatal test. Therefore, the results of karyotyping and FISH were analyzed to determine the percentage of clinically abnormal fetuses which would be missed by using standalone FISH. Amniotic fluid samples from 9033 high-risk pregnancies were subjected to karyotyping and FISH for chromosomes 13, 18, 21, X, and Y. Karyotype and FISH were normal in 8680 (96.1 %) of these samples and 353 (3.9 %) had abnormal karyotypes: 285 (3.2 %) were aneuploidies, also detected by FISH and 68 (0.7 %) were structural chromosomal aberrations not detected by FISH. Out of these 68 structural aberrations, 40 (0.4 %) were balanced rearrangements with no apparent clinical significance and 28 (0.3 %) were unbalanced rearrangements with potential clinical significance. By standalone FISH, 0.3 % clinically-significant samples would have been missed. A 0.2 % risk of procedure-related abortion may be acceptable but a 0.3 % risk of having an abnormal child may not be acceptable to the parents. FISH may be offered as a first test, followed by karyotyping. Although, karyotyping increases the cost, it is preferable to carry this out once an invasive procedure has been opted for, with its accompanying risk of miscarriage.

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Prenatal detection of Down's syndrome by rapid aneuploidy testing for chromosomes 13, 18, and 21 by FISH or PCR without a full karyotype: a cytogenetic risk assessment

Cited by 111 publications

References 19 publications

QF‐PCR as a stand‐alone test for prenatal samples: the first 2 years' experience in the London region

QF‐PCR as a stand‐alone test for prenatal samples: the first 2 years' experience in the London region

Rapid aneuploidy detection with multiplex ligation-dependent probe amplification: a prospective study of 4000 amniotic fluid samples

FISH is not Suitable as a Standalone Test for Detecting Fetal Chromosomal Abnormalities

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