Array comparative genomic hybridization in prenatal diagnosis of first trimester pregnancies at high risk for chromosomal anomalies

Molecular Cytogenetics

Peter Miny¹  Sevgi Tercanli³  Karl Heinimann¹  Friedel Wenzel¹  Vanessa Klug¹  Anjeung Kang³  Isabel Filges² 

[1]Dr. med. Isabel Filges, Division of Medical Genetics, University Children’s Hospital and Department of Biomedicine, University of Basel, Burgfelderstrasse 101, Building J, CH-4055, Basel, Switzerland

[2]Department of Medical Genetics, BC Children’s and Women’s Hospital, Child and Family Research Institute, University of British Columbia, Box 153, 4480 Oak Street, Vancouver, BC V6H 3V4, Canada

[3]Ultrasound Unit, Department of Obstetrics and Gynecology, University Hospital, Basel, Switzerland

关键词: CVS;    High risk;    First trimester;    aCGH;    ArrayCGH;    Array comparative genomic hybridization;    Prenatal diagnosis;   

Others  :  1151292
DOI  :  10.1186/1755-8166-5-38

 received in 2012-05-31, accepted in 2012-07-30,  发布年份 2012

【 摘 要 】

Objective

To describe the diagnostic performance of array comparative genomic hybridization (aCGH) as a potential first line diagnostic method in first trimester high risk pregnancies.

Method

In a retrospective study we performed aCGH using a targeted array BAC platform (Constitutional Chip® 4.0, PerkinElmer, Turku Finland, median resolution 600 kB) and the Affymetrix Cytogenetics® Whole Genome 2.7 M array (at a resolution of 400kB) on 100 anonymized prenatal samples from first trimester high risk pregnancies with normal conventional karyotype. We studied the technical feasibility and turn-around-time as well as the detection rate of pathogenic submicroscopic chromosome anomalies and CNVs of unknown significance.

Results

We obtained results in 98 of 100 samples in 3 to a maximum of 5 days after DNA extraction. At the given resolution we did not identify any additional pathogenic CNVs but two CNVs of unknown significance in the chromosomal regions 1q21.1q21.2 (deletion) and 5p15.33 (duplication) (2%).

Conclusion

In accordance with a growing number of reports this study supports the concept that aCGH at a resolution of 400-600kB may be used as a first line prenatal diagnostic test with high diagnostic safety and rapid turn-around time in high-risk first trimester pregnancies. Detection rate of CNVs of unknown significance, considered as a major hindrance for replacing conventional karyotyping by aCGH, is 2%, but the diagnosis of additional submicroscopic anomalies in this heterogeneous group of patients seems to be rare.

【 授权许可】

   
2012 Filges et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Ekelund C, Jørgensen F, Petersen O, Sundberg K, Tabor A: Impact of a new national screening policy for Down's syndrome in Denmark: population based cohort study. BMJ 2008, 337:a2547.
• [2]Lichtenbelt KD, Alizadeh BZ, Scheffer PG, Stoutenbeek P, Schielen PC, Page-Christiaens LC, Schuring-Blom GH: Trends in the utilization of invasive prenatal diagnosis in The Netherlands during. Prenat Diagn 2000–2009, 31(8):765-772.
• [3]Chen EZ, Chiu RW, Sun H, Akolekar R, Chan KC, Leung TY, Jiang P, Zheng YW, Lun FM, Chan LY, Jin Y, Go AT, Lau ET, To WW, Leung WC, Tang RY, Au-Yeung SK, Lam H, Kung YY, Zhang X, van Vugt JM, Minekawa R, Tang MH, Wang J, Oudejans CB, Lau TK, Nicolaides KH, Lo YM: Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PLoS One 2011, 6(7):e21791.
• [4]Liao GJ, Lun FM, Zheng YW, Chan KC, Leung TY, Lau TK, Chiu RW, Lo YM: Targeted massively parallel sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles. Clin Chem 2011, 57(1):92-101.
• [5]Lo YM, Chan KC, Sun H, Chen EZ, Jiang P, Lun FM, Zheng YW, Leung TY, Lau TK, Cantor CR, Chiu RW: Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med 2010, 2(61):61. ra91
• [6]Chiu RW, Akolekar R, Zheng YW, Leung TY, Sun H, Chan KC, Lun FM, Go AT, Lau ET, To WW, Leung WC, Tang RY, Au-Yeung SK, Lam H, Kung YY, Zhang X, van Vugt JM, Minekawa R, Tang MH, Wang J, Oudejans CB, Lau TK, Nicolaides KH, Lo YM: Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011, 342:c7401.
• [7]Chiu RW, Lo YM: Non-invasive prenatal diagnosis by fetal nucleic acid analysis in maternal plasma: the coming of age. Semin Fetal Neonatal Med 2011, 16(2):88-93.
• [8]Papageorgiou EA, Karagrigoriou A, Tsaliki E, Velissariou V, Carter NP, Patsalis PC: Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nat Med 2011, 17(4):310-313.
• [9]Miller DT: Genetic testing for autism: recent advances and clinical implications. Expert Rev Mol Diagn 2010, 10(7):837-840.
• [10]Manning M, Hudgins L: Committee PPaG. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 2010, 12(11):742-745.
• [11]Vialard F, Molina Gomes D, Leroy B, Quarello E, Escalona A, Le Sciellour C, Serazin V, Roume J, Ville Y, de Mazancourt P, Selva J: Array Comparative Genomic Hybridization in Prenatal Diagnosis: Another Experience. Fetal Diagn Ther 2009, 25(2):277-284.
• [12]Van den Veyver I, Patel A, Shaw C, Pursley A, Kang S, Simovich M, Ward P, Darilek S, Johnson A, Neill S, Bi W, White L, Eng C, Lupski J, Cheung S, Beaudet A: Clinical use of array comparative genomic hybridization (aCGH) for prenatal diagnosis in 300 cases. Prenat Diagn 2009, 29(1):29-39.
• [13]Tyreman M, Abbott K, Willatt L, Nash R, Lees C, Whittaker J, Simonic I: High resolution array analysis: diagnosing pregnancies with abnormal ultrasound findings. J Med Genet 2009, 46(8):531-541.
• [14]Faas BH, van der Burgt I, Kooper AJ, Pfundt R, Hehir-Kwa JY, Smits AP, de Leeuw N: Identification of clinically significant, submicroscopic chromosome alterations and UPD in fetuses with ultrasound anomalies using genome-wide 250 k SNP array analysis. J Med Genet 2010, 47(9):586-594.
• [15]Friedman J: High-resolution array genomic hybridization in prenatal diagnosis. Prenat Diagn 2009, 29(1):20-28.
• [16]Bui TH, Vetro A, Zuffardi O, Shaffer LG: Current controversies in prenatal diagnosis 3: is conventional chromosome analysis necessary in the post-array CGH era? Prenat Diagn 2011, 31(3):235-243.
• [17]Committee ACOG: Opinion No. 446: array comparative genomic hybridization in prenatal diagnosis. Obstet Gynecol 2009, 114(5):1161-1163.
• [18]Manegold G, Tercanli S, Struben H, Huang D, Kang A: Is a Routine Ultrasound in the Third Trimester Justified? - Additional Fetal Anomalies Diagnosed After Two Previous Unremarkable Ultrasound Examinations. Ultraschall Med 2011, 32(4):381.
• [19]Hauge X, Raca G, Cooper S, May K, Spiro R, Adam M, Martin CL: Detailed characterization of, and clinical correlations in, 10 patients with distal deletions of chromosome 9p. Genet Med 2008, 10(8):599-611.
• [20]Filges I, Kang A, Klug V, Wenzel F, Heinimann K, Tercanli S, Miny P: aCGH on chorionic villi mirrors the complexity of fetoplacental mosaicism in prenatal diagnosis. Prenat Diagn 2011, 31(5):473-478.
• [21]Leung TY, Vogel I, Lau TK, Chong W, Hyett JA, Petersen OB, Choy KW: Identification of submicroscopic chromosomal aberrations in fetuses with increased nuchal translucency and an apparently normal karyotype. Ultrasound Obstet Gynecol 2011, 38(3):307-310.
• [22]Pergament E, Alamillo C, Sak K, Fiddler M: Genetic assessment following increased nuchal translucency and normal karyotype. Prenat Diagn 2011, 31(3):307-310.
• [23]Houweling AC, de Mooij YM, van der Burgt I, Yntema HG, Lachmeijer AM, Go AT: Prenatal detection of Noonan syndrome by mutation analysis of the PTPN11 and the KRAS genes. Prenat Diagn 2010, 30(3):284-286.
• [24]Lee KA, Williams B, Roza K, Ferguson H, David K, Eddleman K, Stone J, Edelmann L, Richard G, Gelb BD, Kornreich R: PTPN11 analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings. Clin Genet 2009, 75(2):190-194.
• [25]Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH: 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(5):749-764.
• [26]D`Amours G, Kibar Z, Mathonnet G, Fetni R, Tihy F, Désilets V, Nizard S, Michaud JL, Lemyre E: Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype. Clin Genet 2012, 81(2):128-141.
• [27]Srebniak M, Boter M, Oudesluijs G, Joosten M, Govaerts L, Van Opstal D, Galjaard RJ: Application of SNP array for rapid prenatal diagnosis: implementation, genetic counselling and diagnostic flow. Eur J Hum Genet 2011, 19(12):1230-1237.
• [28]Kleeman L, Bianchi D, Shaffer L, Rorem E, Cowan J, Craigo S, Tighiouart H, Wilkins-Haug L: Use of array comparative genomic hybridization for prenatal diagnosis of fetuses with sonographic anomalies and normal metaphase karyotype. Prenat Diagn 2009, 29(13):1213-1217.
• [29]Coppinger J, Alliman S, Lamb A, Torchia B, Bejjani B, Shaffer L: Whole-genome microarray analysis in prenatal specimens identifies clinically significant chromosome alterations without increase in results of unclear significance compared to targeted microarray. Prenat Diagn 2009, 29(12):1156-1166.
• [30]Sahoo T, Cheung S, Ward P, Darilek S, Patel A, del Gaudio D, Kang S, Lalani S, Li J, McAdoo S, Burke A, Shaw C, Stankiewicz P, Chinault A, Van den Veyver I, Roa B, Beaudet A, Eng C: Prenatal diagnosis of chromosomal abnormalities using array-based comparative genomic hybridization. Genet Med 2006, 8(11):719-727.
• [31]Maya I, Davidov B, Gershovitz L, Zalzstein Y, Taub E, Coppinger J, Shaffer LG, Shohat M: Diagnostic utility of array-based comparative genomic hybridization (aCGH) in a prenatal setting. Prenat Diagn 2010, 30(12–13):1131-1137.
• [32]Hillman SC, Pretlove S, Coomarasamy A, McMullan DJ, Davison EV, Maher ER, Kilby MD: 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(1):6-14.
• [33]Filges I, Suda L, Weber P, Datta AN, Fischer D, Dill P, Glanzmann R, Benzing J, Hegi L, Wenzel F, Huber AR, Mori AC, Miny P, Röthlisberger B: High resolution array in the clinical approach to chromosomal phenotypes. Gene 2012, 495(2):163-169. 10
• [34]Rodriguez-Revenga L, Mila M, Rosenberg C, Lamb A, Lee C: Structural variation in the human genome: the impact of copy number variants on clinical diagnosis. Genet Med 2007, 9(9):600-606.
• [35]Lee C, Iafrate A, Brothman A: Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat Genet 2007, 39(7 Suppl):S48-S54.
• [36]Carter NP: Methods and strategies for analyzing copy number variation using DNA microarrays. Nat Genet 2007, 39(7 Suppl):S16-S21.
• [37]Vermeesch JR, Fiegler H, de Leeuw N, Szuhai K, Schoumans J, Ciccone R, Speleman F, Rauch A, Clayton-Smith J, Van Ravenswaaij C, Sanlaville D, Patsalis PC, Firth H, Devriendt K, Zuffardi O: Guidelines for molecular karyotyping in constitutional genetic diagnosis. Eur J Hum Genet 2007, 15(11):1105-1114.