Dataset Information

Integrated FISH, Karyotyping and aCGH Analyses for Effective Prenatal Diagnosis of Common Aneuploidies and Other Cytogenomic Abnormalities.

ABSTRACT: Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements, and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridization (aCGH). Of the 386 cases retrieved from the past decade, common aneuploidies were detected in 137 cases (35.5%), other chromosomal structural rearrangements were detected in four cases (1%), and pCNV were detected in five cases (1.3%). The relative frequencies for common aneuploidies suggested an under detection of sex chromosome aneuploidies. Approximately 9.5% of cases with common aneuploidies showed a mosaic pattern. Inconsistent results between FISH and karyotyping were noted in cases with pseudo-mosaicism introduced by culture artifact or variable cellular proliferation from cells with mosaic karyotypic complements under in vitro cell culture. Based on findings from this case series, cell-based FISH and karyotyping should be performed to detect common aneuploidies, structural chromosomal abnormalities, and mosaic pattern. DNA-based aCGH and reflex FISH should be performed to detect and confirm genomic imbalances and pCNV. Practice points to ensure the diagnostic accuracy and efficacy were summarized.

SUBMITTER: Chai H

PROVIDER: S-EPMC6410168 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Integrated FISH, Karyotyping and aCGH Analyses for Effective Prenatal Diagnosis of Common Aneuploidies and Other Cytogenomic Abnormalities.

Chai Hongyan H DiAdamo Autumn A Grommisch Brittany B Boyle Jennifer J Amato Katherine K Wang Dongmei D Wen Jiadi J Li Peining P

Medical sciences (Basel, Switzerland) 20190123 2

Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements, and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridizati ...[more]

PMID: 30678103

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Project description:BackgroundThe aims of this study were to evaluate the clinical utility of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH) analyses on prenatal cases and to review prenatal ultrasound findings of cytogenomic syndromes.ResultsOf the 54 prenatal cases analyzed, cytogenomic abnormalities were characterized in 14 cases. In four fetuses with abnormal ultrasound findings, a 40.701 Mb duplication of 8q22.3-q24.3 and a 23.839 Mb deletion of 7q33-q36.3 derived from a paternal balanced translocation, a de novo 13.062 Mb deletion of 11q24.1-q25 for Jacobsen syndrome, a de novo 19.971 Mb deletion of 7q11.23-q21.3 for type 1 split-hand/foot malformation (SHFM1), and a de novo 28.909 Mb duplication of 3q21.1-q25.1 were detected. A 699.8 Kb deletion at 5p15.33 for Cri du Chat syndrome was confirmed in a fetus with abnormal MLPA result. A fetus with abnormal maternal screening was detected with a de novo distal 1.747 Mb duplication at 2q37.1-q37.2 and a 6.664 Mb deletion at 2q37.2-q37.3. Of the eight cases referred by history of spontaneous abortions, derivative chromosomes 11 from paternal carriers of a balanced 8q/11q and a 10q/11q translocation were noted in two cases, simple aneuploids of trisomy 2 and trisomy 21 were seen in three cases, and compound aneuploids of two or three chromosomes were found in three cases. Post-test genetic counseling was performed with detailed genomic information and well characterized postnatal syndromic features.ConclusionsThese results demonstrated that coupling MLPA screening and aCGH analysis are a cost-effective approach to detect cytogenomic abnormalities in a prenatal setting. The aCGH analysis provided not only genomic maps of breakpoints and gene content of imbalanced regions but also better inference of related phenotypes for genetic counseling. Prenatal ultrasound findings reported in the literature for Jacobsen syndrome, SHFM and Cri du Chat syndrome were summarized for use as diagnostic references.

Project description:Background: Array comparative genomic hybridization (aCGH), karyotyping and fluorescence in situ hybridization (FISH) analyses have been used in a clinical cytogenetic laboratory. A systematic analysis on diagnostic findings of cytogenomic abnormalities in current prenatal and pediatric settings provides approaches for future improvement. Methods: A retrospective analysis was performed on abnormal findings by aCGH, karyotyping, and FISH from 3,608 prenatal cases and 4,509 pediatric cases during 2008-2017. The diagnostic accuracy was evaluated by comparing the abnormality detection rate (ADR) and the relative frequency (RF) of different types of cytogenomic abnormalities between prenatal and pediatric cases. A linear regression correlation between known prevalence and ADR of genomic disorders was used to extrapolate the prevalence of other genomic disorders. The diagnostic efficacy was estimated as percentage of detected abnormal cases by expected abnormal cases from served population. Results: The composite ADR for numerical chromosome abnormalities, structural chromosome abnormalities, recurrent genomic disorders, and sporadic pathogenic copy number variants (pCNVs) in prenatal cases were 13.03%, 1.77%, 1.69%, and 0.9%, respectively, and were 5.13%, 2.84%, 7.08%, and 2.69% in pediatric cases, respectively. The chromosomal abnormalities detected in prenatal cases (14.80%) were significantly higher than that of pediatric cases (7.97%) (p < 0.05), while the pCNVs detected in prenatal cases (2.59%) were significantly lower than that of pediatric cases (9.77%) (p < 0.05). The prevalence of recurrent genomic disorders and total pCNVs was estimated to be 1/396 and 1/291, respectively. Approximately, 29% and 35% of cytogenomic abnormalities expected from the population served were detected in current prenatal and pediatric diagnostic practice, respectively. Conclusion: For chromosomal abnormalities, effective detection of Down syndrome (DS) and Turner syndrome (TS) and under detection of sex chromosome numerical abnormalities in both prenatal and pediatric cases were noted. For pCNVs, under detection of pCNVs in prenatal cases and effective detection of DiGeorge syndrome (DGS) and variable efficacy in detecting other pCNVs in pediatric cases were noted. Extend aCGH analysis to more prenatal cases with fetal ultrasonographic anomalies, enhanced non-invasive prenatal (NIPT) testing screening for syndromic genomic disorders, and better clinical indications for pCNVs are approaches that could improve diagnostic yield of cytogenomic abnormalities.

Project description:BACKGROUND:Population-based prenatal screening has become a common and widely available obstetrical practice in majority of developed countries. Under the patient autonomy principle, women should understand the screening options, be able to take their personal preferences and situations into account, and be encouraged to make autonomous and intentional decisions. The majority of the current research focuses on the prenatal screening uptake rate, women's choice on screening tests, and the influential factors. However, little attention has been paid to women's choice-making processes and experiences in prenatal screening and their influences on choice satisfaction. Understanding women's choice-making processes and experiences in pregnancy and childbirth is the prerequisite for designing women-centered choice aids and delivering women-centered maternity care. This paper presents a pilot study that aims to investigate women's experiences when they make choices for screening tests, quantify the choice-making experience, and identify the experiential factors that affect women's satisfaction on choices they made. METHOD:We conducted a mixed-method research at Helsinki and Uusimaa Hospital District (HUS) in Finland. First, the women's choice-making experiences were explored by semi-structured interviews. We interviewed 28 women who participated in prenatal screening. The interview data was processed by thematic analysis. Then, a cross-sectional self-completion survey was designed and implemented, assessing women's experiences in choice-making and identifying the experiential factors that influence choice satisfaction. Of 940 distributed questionnaires, 185 responses were received. Multivariable linear regression analysis was used to detect the effects of the variables. RESULTS:We developed a set of measurements for women's choice-making experiences in prenatal screening with seven variables: activeness, informedness, confidence, social pressure, difficulty, positive emotion and negative emotion. Regression revealed that activeness in choice-making (??=?0.176; p?=?0.023), confidence in choice-making (??=?0.388; p?<?0.001), perceived social pressure (??=?-?0.306; p?<?0.001) and perceived difficulty (??=?-?0.274; p?<?0.001) significantly influenced women's choice satisfaction in prenatal screening. CONCLUSIONS:This study explores the experiential dimension of women's choice-making in prenatal screening. Our result will be useful for service providers to design women-centered choice environment. Women's willingness and capabilities of making active choices, their preferences, and social reliance should be well considered in order to facilitate autonomous, confident and satisfying choices.

Dataset Information

Integrated FISH, Karyotyping and aCGH Analyses for Effective Prenatal Diagnosis of Common Aneuploidies and Other Cytogenomic Abnormalities.

Publications

Integrated FISH, Karyotyping and aCGH Analyses for Effective Prenatal Diagnosis of Common Aneuploidies and Other Cytogenomic Abnormalities.

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