Microarray application in prenatal diagnosis: a position statement from the cytogenetics working group of the Italian Society of Human Genetics (SIGU), November 2011

Novelli, Antonio; Grati, Francesca Romana; Ballarati, Lucia; Bernardini, Laura; Bizzoco, Domenico; Camurri, Lamberto; Casalone, Rosario; Cardarelli, Laura; Cavalli, Pietro; Ciccone, Roberto; Clementi, M.; Dalprà, Leda; Gentile, Mattia; Gelli, G; Grammatico, Paola; Malacarne, Michela; Nardone, Anna Maria; Pecile, Vanna; Simoni, Giuseppe; Zuffardi, Orsetta; Giardino, Daniela

doi:10.1002/uog.11092

Cited by 58 publications

(54 citation statements)

References 42 publications

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“…As demonstrated in our cohort, these microdeletions and microduplications may not be associated with abnormal ultrasounds, or abnormalities may not be visible until later in the pregnancy, making this test appropriate for low-risk cases. While professional guidelines support the use of microarrays in cases with ultrasound abnormalities [4][5][6] , the microdeletions and microduplications on our panel have been associated with prenatal abnormalities [46][47][48][49][50] , so this test would have added diagnostic capabilities if there are barriers to microarray testing, such as intolerance for VOUS, lack of insurance coverage, or cost (with SPPP costing a little more than one third of a microarray). By only testing for syndromes that are relatively severe and of known phenotypes, we aim to minimize counseling difficulties following abnormal results.…”

Section: Discussionmentioning

confidence: 99%

“…Chromosomal mi-croarrays can be used prenatally to identify such microdeletions and microduplications, as well as some abnormalities >10 Mb that are missed due to the limited resolution of prenatal karyotypes [3] . Current recommendations for prenatal microarray usage are mostly limited to cases with abnormal ultrasound findings, mainly due to the possibility of identifying variants of uncertain significance (VOUS) [4][5][6] . While several recent large studies have addressed the question of microarray's detection of chromosome abnormalities in low-risk pregnant populations [3,[7][8][9] , some individuals likely have a low tolerance for VOUS [10] and, therefore, would benefit from targeted testing aimed at limiting VOUS but interrogating select regions of the genome at a higher resolution than traditional karyotyping.…”

Section: Introductionmentioning

confidence: 99%

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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: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Novelli et al [29] described that single nucleotide polymorphism detection for peripheral blood lymphocytes could identify 9 %-12 % of genovariations in the couples who had normal G-banding karyotype analysis and a history of adverse pregnancy and delivery outcomes.…”

Section: Detection Of Peripheral Blood Lymphocyte Karyotypementioning

confidence: 99%

Karyotype analysis in large-sample infertile couples living in Central China: a study of 14965 couples

Liu

Kong

et al. 2013

J Assist Reprod Genet

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Objective To explore that it is necessary to routinely detect chromosomes in fertile couples, we detected peripheral blood lymphocyte karyotype in 14965 infertile couples living in Central China and analyzed the incidence and type of chromosomal anomaly. Methods G-banding karyotype analysis of peripheral blood lymphocytes was performed in 14965 couples who went to the outpatient department of our reproductive medical center for counseling on infertility between January 2004 and December 2011. Semen analysis was performed three times in all the men from the 14965 couples. Results The rate of chromosomal anomaly in the 14965 infertile couples was 3.84 % (1150/29930). The rate of chromosomal anomaly in the men from 14965 couples was 6.84 % (1024/14965) and in the women 0.84 % (126/14965). The rates of chromosomal anomaly were 1.69 % in normal semen group, 11.82 % in light oligoastheno-spermis group, 6.58 % in moderate to severe oligastheno-spermia group and 17.26 % in azoospermia group. Conclusion Since the rates of chromosomal anomaly are 1.69 % and 11.82 % even in normal semen group and light oligo-astheno-spermia group, respectively, it is necessary to detect peripheral blood lymphocyte karyotype in all infertile couples.

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“…Although equal benefits may be expected for the prenatal diagnosis of chromosome anomalies the conventional microscopic approach has maintained its role as the “gold standard” for the time being [7,8]. The use of microarrays in this setting has been met with caution for various reasons [9,10].…”

Section: Introductionmentioning

confidence: 99%

Chromosomal Microarrays in Prenatal Diagnosis: Time for a Change of Policy?

et al. 2013

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Microarrays have replaced conventional karyotyping as a first-tier test for unbalanced chromosome anomalies in postnatal cytogenetics mainly due to their unprecedented resolution facilitating the detection of submicroscopic copy number changes at a rate of 10–20% depending on indication for testing. A number of studies have addressed the performance of microarrays for chromosome analyses in high risk pregnancies due to abnormal ultrasound findings and reported an excess detection rate between 5% and 10%. In low risk pregnancies, clear pathogenic copy number changes at the submicroscopic level were encountered in 1% or less. Variants of unclear clinical significance, unsolicited findings, and copy number changes with variable phenotypic consequences are the main issues of concern in the prenatal setting posing difficult management questions. The benefit of microarray testing may be limited in pregnancies with only moderately increased risks (advanced maternal age, positive first trimester test). It is suggested to not change the current policy of microarray application in prenatal diagnosis until more data on the clinical significance of copy number changes are available.

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Microarray application in prenatal diagnosis: a position statement from the cytogenetics working group of the Italian Society of Human Genetics (SIGU), November 2011

Abstract: . We are grateful to Prof. Agatino Battaglia, MD for critical revision and improvements to the manuscript.

Cited by 58 publications

References 42 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

Karyotype analysis in large-sample infertile couples living in Central China: a study of 14965 couples

Chromosomal Microarrays in Prenatal Diagnosis: Time for a Change of Policy?

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