Diagnostic Yield of Cytogenomic Abnormalities in Current Prenatal Diagnosis: A Retrospective Analysis in a Clinical Cytogenetics Laboratory

Peining Li, PhD, Autumn DiAdamo, BS, Brittany Grommisch, BS, Jennifer Boyle, MS, Katherine Amato, BS, Dongmei Wang, MS, Hongyan Chai, PhD, MD

Abstract


Background: Chromosome microarray analysis has been the first-tier genetic testing for pediatric patients and an integrated testing for prenatal cases. Aims: The purpose of this study was to evaluate the diagnostic yield from current prenatal genetic clinics and to provide guidance for future improvement on prenatal diagnosis of cytogenomic abnormalities. Material and Methods: A retrospective analysis of abnormal findings from karyotyping and array comparative genomic hybridization (aCGH) analysis of amniotic fluid (AF) specimens and chorionic villi samples (CVS) during the 2012-2015 interval was performed. The diagnostic efficiency as determined by the relative frequencies (RF) of different types of cytogenomic abnormalities was compared between prenatal and pediatric case series. Result: Data retrieved from this four-year interval presented 341 AF and 656 CVS with an annual caseload of 249 cases and an abnormality detection rate (ADR) of 20.2%. A comparison with prenatal testing performed in the 2007-2009 interval noted a 57% reduction of annual caseload and a 67% increase in ADR. While the ADR for structural chromosomal abnormalities remained the same; it was estimated that 80% of the increased ADR resulted from improved detection of numerical chromosomal abnormalities and 20% were from submicroscopic genomic aberrations detected by aCGH analysis. The RF for numerical chromosome abnormalities, structural chromosomal abnormalities, microdeletion and microduplication syndromes, and other genomic aberrations were 83.5%, 9%, 3.5% and 4% for the prenatal cases and 8.5%. 9.7%, 37.5% and 44.3% for a pediatric case series, respectively. Similar frequency in the detection of structural chromosomal abnormalities and striking different frequencies in other types of abnormalities were noted. Conclusion: These results indicated that the current prenatal diagnosis is effective in detecting chromosomal abnormalities but has a limitation on detecting genomic aberrations. Better correlations of ultrasonagraphic fetal anomalies and maternal serum fetal DNA quantitation with genomic aberrations are needed to improve prenatal cytogenomic analysis.

[N A J Med Sci. 2016;9(4):136-140.   DOI:  10.7156/najms.2016.0904136]

 

Key Words: prenatal diagnosis, array comparative genomic hybridization, chromosomal abnormalities,

microdeletion/duplication syndromes, pathogenic copy number variants, diagnostic yield


Full Text:

PDF TEXT

References


Benn P, Egan JF, Fang M, Smith-Bindman R. Changes in the utilization of prenatal diagnosis. Obstet Gynecol. 2004;103:1255-1260.

Li P, Pomianowski P, DiMaio SM, et al. Genomic characterization of prenatally detected chromosomal structural abnormalities using oligonucleotide array comparative genomic hybridization. Am J Med Genet. 2011;155A:1605-1615.

Chiu RW, Chan KC, Gao Y, et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA. 2008;105:20458-20463.

Xu ZY, Xie JS, Meng JL, Li P, Pan XH, Zhou QH. Non-invasive prenatal diagnosis: A comparison of cell free fetal DNA (cffDNA) based screening and fetal nucleated red blood cell (fnRBC) initiated testing. N A J Med Sci. 2013;6:194-199.

Benn P. Non-invasive prenatal testing using cell free DNA in maternal plasma: Recent developments and future prospects. J Clin Med. 2014;3:537-565.

Meng JL, Matarese C, Crivello J, et al. Changes in and efficacies of indications for invasive prenatal diagnosis of cytogenomic abnormalities: 13 years of experience in a single center. Med Sci Monit. 2015;21:1942-1948.

Benn P, Borrell A, Chiu RW, et al. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn. 2015;32:725-734.

Xu ZY, Geng Q, Luo FW, Xu F, Li P, Xie JS. Multiplex ligation-dependent probe amplification and array comparative genomic hybridization analyses for prenatal diagnosis of cytogenomic abnormalities. Mol Cytogenet. 2014;7:84.

Cui C, Shu W, Li P. Fluorescence in situ hybridization: cell-based genetic diagnostic and research applications. Front Cell Dev Biol. 2016;4:89.

Xiang B, Li A, Valentin D, Novak N, Zhao HY, Li P. Analytical and clinical validity of whole genome oligonucleotide array comparative genomic hybridization for pediatric patients with mental retardation and developmental delay. Am J Med Genet. 2008;146A:1942-1954.

Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749-764.

Xiang B, Zhu H, Shen Y, et al. Genome-wide oligonucleotide array CGH for etiological diagnosis of mental retardation: A multi-center experience of 1,499 clinical cases. J Mol Diagn. 2010;12:204-212.

Wei Y, Xu F, Li P. Technology-driven and evidence-based genomic analysis for integrated pediatric and prenatal genetic evaluation. J Genet Genomics. 2013;40:1-14.

Li P, Xu F, Shu W. The spectrum of cytogenomic abnormalities in patients with developmental delay and intellectual disabilities. N A J Med Sci. 2015;8:166-172.

Zhou QH, Wu S-Y, Amato K, Diadamo A, Li P. Spectrum of cytogenomic abnormalities revealed by array comparative genomic hybridization in products of conception culture failure and normal karyotype samples. J Genet Genomics. 2016;43:121-131.

Wei Y, Gao XF, Yan LY, Xu F, Li P, Zhao YY. Prenatal diagnosis and postnatal follow up of partial trisomy 13q and partial monosomy 10p: A case report and review of the literature. Case Rep Genet. 2012:821347.

Cook S, Wilcox K, Grommisch B, Li P, Xu F. Prenatal diagnosis of Xq26.1-q26.3 duplication in two fetuses of a woman with gonadal mosaicism. N A J Med Sci. 2014;7:176-179.

DiMaio SM, Yang H, Mahoney M, McGrath J, Li P. Familial deletions of the GPC3 and GPC4 genes associated with Simpson-Golabi-Behmel syndrome. Meta Gene. 2016. doi:10.1016/j.mgene.2016.08.008.

ACOG Committee Opinion No. 446: array comparative genomic hybridization in prenatal diagnosis. Obstet Gynecol. 2009;114:1161-1163.

South ST, Lee C, Lamb AN, et al. Working Group for the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med. 2013;15:901-909.

Xu F, Li L, Schulz VP, Gallagher PG, Xiang B, Zhao H, et al. Cytogenomic mapping and bioinformatic mining reveal interacting brain expressed genes for intellectural disabilities. Mol Cytogenet. 2014;7:4.

Xiang B, Hemingway S, Qumsiyeh M, Li P. CytoAccess: A relational laboratory information management system for a clinical cytogenetics laboratory. J Assoc Genet Technol. 2006;32:168-170.

Xiang B, Xu F, Zeng W, Zi D, Ma D. Navigating web-based resources for genetic testing of chromosome abnormalities, CNVs and gene mutations. N A J Med Sci. 2014;7:163-170.

Cheung SW, Shaw CA, Scott DA, et al. Microarray-based CGH detects chromosomal mosaicism not revealed by conventional cytogenetics. Am J Med Genet. 2007;143A:1679-1686.

Hall GK, Mackie FL, Hamilton S, Evans A, McMullan DJ, Williams D, et al. Chromosomal microarray analysis allows prenatal detection of low level mosaic autosomal aneuploidy. Prenat Diagn. 2014;34(5):505-507.

Cheng LE, Wiita A, Zhongxia Qi Z, Yu J. Challenges in prenatal cytogenomic microarray reporting: balancing laboratory findings, clinical utility and patient anxiety. N A J Med Sci. 2014;7:148-155.

Hillman SC, Pretlove S, Coomarasamy A, et al. Additional information from array comparative genomic hybridization technology over conventional karyotyping in prenatal diagnosis: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2011;37:6-14.

Fiorentino F, Caiazzo F, Napolitano S, et al. Introducing array comparative genomic hybridization into routine prenatal diagnosis practice: a prospective study on over 1000 consecutive clinical cases. Prenat. Diagn. 2011;31:1270-1282.

Lee CN, Lin SY, Lin CH, Shih JC, Lin TH, Su YN. Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies. BJOG. 2012;119:614-625.

Breman A, Pursley AN, Hixson P, et al., Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature. Prenat Diagn. 2012;32:351-361.

Bornstein E, Berger S, Cheung SW, et al. Universal prenatal chromosomal microarray analysis: additive value and clinical dilemmas in fetuses with a normal karyotype. Am J Perinatol. 2016. [Epub ahead of print]

Wapner RJ, Babiarz JE, Levy B, et al. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes. Am J Obstet Gynecol. 2015;212:332.e1-9.


Refbacks

  • There are currently no refbacks.