Prenatal diagnosis of chromosomal abnormalities using array-based comparative genomic hybridization

Abstract

Purpose: This study was designed to evaluate the feasibility of using a targeted array-CGH strategy for prenatal diagnosis of genomic imbalances in a clinical setting of current pregnancies. Methods: Women undergoing prenatal diagnosis were counseled and offered array-CGH (BCM V4.0) in addition to routine chromosome analysis.Array-CGH was performed with DNA directly from amniotic fluid cells with whole genome amplification, on chorionic villus samples with amplification as necessary, and on cultured cells without amplification. Results: Ninety-eight pregnancies (56 amniotic fluid and 42 CVS specimens) were studied with complete concordance between karyotype and array results, including 5 positive cases with chromosomal abnormalities. There was complete concordance of array results for direct and cultured cell analysis in 57 cases tested by both methods. In 12 cases, the array detected copy number variation requiring testing of parental samples for optimal interpretation. Array-CGH results were available in an average of 6 and 16 days for direct and cultured cells, respectively. Patient acceptance of array-CGH testing was 74%. Conclusion: This study demonstrates the feasibility of using array-CGH for prenatal diagnosis, including reliance on direct analysis without culturing cells. Use of array-CGH should increase the detection of abnormalities relative to the risk, and is an option for an enhanced level of screening for chromosomal abnormalities in high risk pregnancies. Genet Med 2006:8(11):719-727.

Chromosomal microarray analysis as a first-line test in pregnancies with a priori low risk for the detection of submicroscopic chromosomal abnormalities

“…[37][38][39] At present, numerous independent prospective studies, [17][18][19][22][23][24][26][27][28][29][30] involving the use of various strategies and validated with several different array platforms, have demonstrated the effectiveness and usefulness of CMA in prenatal diagnosis compared to conventional karyotyping.…”

“…Although several previously reported retrospective and prospective studies [15][16][17][18][19][20][21][22][23][24] have demonstrated the effectiveness and usefulness of CMA in clinical prenatal diagnosis, only limited conclusions could be drawn due to the small size of the cohorts analyzed. These studies have all provided reassuringly consistent results in terms of analytical validity, clinical validity and clinical utility of the technique applied in the prenatal diagnosis setting, compared to traditional karyotyping.…”

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

“…In addition, array-based CGH can detect chromosome aberrations at 50-100 kb resolution and link changes in an offspring's clinical phenotype and function with specific chromosomal duplications and deletions. These attributes have been used successfully in human prenatal testing [Sahoo et al, 2006], but the applications of CGH to the analyses of environmentally induced heritable effects remains to be established.…”

The ‘thousand-dollar genome’: an ethical exploration

“…If other parties [68][69][70] then propose a broader test, this is essentially a plea for additional prenatal screening * , to be offered to women who already qualify for a (expensive and not entirely riskfree) chorion villus sampling or amniocentesis due to an elevated risk of having a child with Down syndrome. In the United States, where women without an elevated risk of having a child with Down syndrome (or a specific indication for prenatal diagnostic testing) who want to be tested can undergo a chorion villus sampling or amniocentesis 71 , this type of array screening could become available to all pregnant women (who can afford it).…”

“…The women who rejected the test did so because they were afraid of additional worries, and because they felt the additional conditions that might be found were extremely rare. 68,77,78 Of course, array CGH is not the same thing as a full sequence analysis, but as soon as the costs of whole genome sequencing no longer present a barrier, it is not unlikely that further expansion in that direction will be advocated. Those who want to obtain (and to provide) 'as much information as possible about the foetus' will eventually no longer be happy with anything less than the complete genome.…”