Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases

Papoulidis, Ioannis; Sotiriadis, Alexandros; Siomou, Elisavet; Papageorgiou, Elena; Eleftheriades, Makarios; Papadopoulos, Vasilios; Oikonomidou, Eirini; Orrù, Sandro; Manolakos, Emmanouil; Athanasiadis, Apostolos

doi:10.1002/pd.4685

Cited by 27 publications

(25 citation statements)

References 31 publications

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“…Our results showed a higher percentage of VOUS in comparison to reported studies, where the detection rate ranged from 0.5 to 1.7% [Brady et al, 2014;Papoulidis et al, 2015]. This discrepancy may be due to (a) VOUS definition, considering that some groups do not report rearrangements containing no genes [Brady et al, 2014]; (b) array resolution (e.g.…”

Section: Discussioncontrasting

confidence: 55%

“…In the recent years, about 20 studies have examined the potential impact/pathogenicity of CNVs in fetal malformations in a prenatal diagnostic setting or after terminations of pregnancy [de Wit et al, 2014;Papoulidis et al, 2015;Srebniak et al, 2015]. The proportion of clinically relevant findings is highly variable (from 4.3 to 18%) [de Wit et al, 2014;Papoulidis et al, 2015;Srebniak et al, 2015], reaching 24% with our study.…”

Section: Discussionsupporting

confidence: 54%

“…The proportion of clinically relevant findings is highly variable (from 4.3 to 18%) [de Wit et al, 2014;Papoulidis et al, 2015;Srebniak et al, 2015], reaching 24% with our study. Discrepancies among studies may be due to different technical platforms, different selection criteria, the size of the sample, or the inclusion of VOUS among the identified CNVs.…”

Section: Discussionsupporting

confidence: 52%

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Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications

Gregorio

Gai²,

Botta³

et al. 2015

Cytogenet Genome Res

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Karyotyping and aCGH are routinely used to identify genetic determinants of major congenital malformations (MCMs) in fetal deaths or terminations of pregnancy after prenatal diagnosis. Pathogenic rearrangements are found with a variable rate of 9-39% for aCGH. We collected 33 fetuses, 9 with a single MCM and 24 with MCMs involving 2-4 organ systems. aCGH revealed copy number variants in 14 out of 33 cases (42%). Eight were classified as pathogenic which account for a detection rate of 24% (8/33) considering fetuses with 1 or more MCMs and 33% (8/24) taking into account fetuses with multiple malformations only. Three of the pathogenic variants were known microdeletion syndromes (22q11.21 deletion, central chromosome 22q11.21 deletion, and TAR syndrome) and 5 were large rearrangements, adding up to >11 Mb per subject and comprising strong phenotype-related genes. One of those was a de novo complex rearrangement, and the remaining 4 duplications and 2 deletions were 130-900 kb in size, containing 1-7 genes, and were classified as variants of unknown clinical significance. Our study confirms aCGH as a powerful technique to ascertain the genetic etiology of fetal major congenital malformations.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionsupporting

confidence: 54%

Section: Discussionsupporting

confidence: 52%

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Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications

Gregorio

Gai²,

Botta³

et al. 2015

Cytogenet Genome Res

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“…It has been previously reported that the screen positive group of combined testing includes cases with abnormalities that were not initially targeted and that are incidentally detected, such as other trisomies, sex aneuploidies, deletions, duplications, mosaicisms and others, and these defects accounted for about 10% of all aneuploidies in our study. Two recent studies analysed data on microarray‐CGH results in a large number of pregnancies undergoing prenatal invasive testing for a variety of reasons, such as maternal age >35 years, high risk from combined testing or second trimester serum screening, maternal request and others . In the group of pregnancies with a high risk from aneuploidy screening, the authors reported an overall incidence of copy number variations with known clinical significance or potential clinical significance of about 1%, which is similar to what was observed in our population (Table ).…”

Section: Discussionmentioning

confidence: 99%

Cell-free DNA testing in the maternal blood in high-risk pregnancies after first-trimester combined screening

et al. 2016

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Objective The objective of this study was to investigate a strategy for clinical implementation of cell-free DNA (cfDNA) testing in high-risk pregnancies after first-trimester combined screening.Methods In 259 singleton pregnancies undergoing invasive testing after first-trimester combined screening, a maternal blood sample was sent to the laboratory Natera for cfDNA testing using a single-nucleotide polymorphismbased methodology.Results The cfDNA test provided a result in 249 (96.1%) pregnancies and, among these, identified as being at high risk 35 of 36 cases of trisomy 21, 13 of 13 with trisomy 18, five of five with trisomy 13 and three of four with sex chromosome aneuploidies. A policy of performing an invasive test in women with a combined risk of ≥1 in 10 or NT ≥4 mm and offering cfDNA testing to the remaining cases would detect all cases of trisomy 21, 18 or 13, 80% of sex aneuploidies and 62.5% of other defects and would avoid an invasive procedure in 82.4% of euploid fetuses. ConclusionIn high-risk pregnancies after combined screening, a policy of selecting a subgroup for invasive testing and another for cfDNA testing would substantially reduce the number of invasive procedures and retain the ability to diagnose most of the observed aneuploidies.

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“…The couple also have a daughter with severe intellectual disability, while most of the daughter's cousins from the father's side have abnormal phenotypes. aCGH technique has an incremental yield over conventional cytogenetics of 0.9-1.6%, which has been mostly highlighted in cases of fetuses with structural defects [Papoulidis et al, 2015]. The use of aCGH was crucial for this case to delineate the exact genotype of the fetus and to coordinate genetic counseling.…”

mentioning

confidence: 99%

7q Deletion/12q Duplication Is the Possible Cause of an Alobar Holoprosencephaly Case

Paspaliaris

Vrachnis²,

Iliodromiti

et al. 2017

Mol Syndromol

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Holoprosencephaly (HPE) spectrum disorder is the most common congenital malformation of the human brain with absence of or incomplete midline cleavage. Its cause is heterogenic, making genetic counseling a challenge. In this case report, a pregnancy affected by alobar HPE is described. Using aCGH, an 8.9-Mb deletion at 7q36.1q36.3 together with a 4.9-Mb duplication at 12q24.32q24.33 is assumed to be the possible reason for this alobar HPE case. It is discussed that disruption of key elements of the developing brain, taking environmental factors into account, contributes to the HPE spectrum. The use of aCGH for invasive prenatal testing is starting to become the standard technique, providing accurate information about the cause of congenital diseases for couples receiving genetic counseling.

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Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases

Abstract: The present study indicates that routine implementation of aCGH offers an incremental yield over conventional karyotype analysis, which is also present in cases with 'milder' indications, further supporting its use as a first-tier test.

Cited by 27 publications

References 31 publications

Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications

Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications

Cell-free DNA testing in the maternal blood in high-risk pregnancies after first-trimester combined screening

7q Deletion/12q Duplication Is the Possible Cause of an Alobar Holoprosencephaly Case

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