Copy number variant; Guidelines; Incidental finding; Prenatal diagnosis; Prenatal microarray; Variant of unknown significance
Abstract :
[en] After their successful introduction in postnatal testing, genome-wide arrays are now rapidly replacing conventional karyotyping in prenatal diagnostics. While previous studies have demonstrated the advantages of this method, we are confronted with difficulties regarding the technology and the ethical dilemmas inherent to genomic arrays. These include indication for testing, array design, interpretation of variants and how to deal with variants of unknown significance and incidental findings. The experiences with these issues reported in the literature are most often from single centres. Here, we report on a national consensus approach how microarray is implemented in all genetic centres in Belgium. These recommendations are subjected to constant re-evaluation based on our growing experience and can serve as a useful tool for those involved in prenatal diagnosis.
Disciplines :
Genetics & genetic processes
Author, co-author :
Vanakker, Olivier
Vilain, Catheline
Janssens, Katrien
Van der Aa, Nathalie
Smits, Guillaume
Bandelier, Claude
Blaumeiser, Bettina
BULK, Saskia ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
CABERG, Jean-Hubert ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
De Leener, Anne
De Rademaeker, Marjan
de Ravel, Thomy
Desir, Julie
Destree, Anne
Dheedene, Annelies
GAILLEZ, Stephanie ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Bachmann-Gagescu R., Mefford H.C., Cowan C., Glew G.M., Hing A.V., Wallace S., et al. Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genet Med 2010, 12:641-647.
Benn P.A. Prenatal counseling and the detection of copy-number variants. Genet Med 2013, 15:316-317.
Bernhardt B.A., Soucier D., Hanson K., Savage M.S., Jackson L., Wapner R.J. Women's experiences receiving abnormal prenatal chromosomal microarray testing results. Genet Med 2013, 15:139-145.
Cooper G.M., Coe B.P., Girirajan S., Rosenfeld J.A., Vu T., Baker C., et al. Acopy number variation morbidity map of developmental delay. Nat Genet 2011, 43:838-846.
Coppinger J., Alliman S., Lamb A.N., Torchia B.S., Bejjani B.A., Schafer L.G. 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, 29:1156-1166.
Decramer S., Parant O., Beaufils S., Clauin S., Guillou C., Kessler S., et al. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. JAm Soc Nephrol. 2007, 18:923-933.
Dondorp W., Sikkema-Raddatz B., de Die-Smulders C., de Wert G. Arrays in postnatal and prenatal diagnosis: an exploration of the ethics of consent. Hum Mutat 2012, 33:916-922.
Dorschner M.O., Amendola L.M., Turner E.H., Robertson P.D., Shirts B.H., Gallego C.J., et al. Actionable, pathogenic incidental findings in 1000 participants' exomes. Am J Hum Genet 2013, 93:631-640.
Draaken M., Reutter H., Schramm C., Bartels E., Boemers T.M., Ebert A.K., et al. Microduplications at 22q11.21 are associated with non-syndromic classic bladder exstrophy. Eur J Med Genet 2010, 53:55-60.
Evangelidou P., Alexandrou A., Moutafi M., Ioannides M., Antoniou P., Koumbaris G., et al. Implementation of high resolution whole genome array CGH in the prenatal clinical setting: advantages, challenges, and review of the literature. Biomed Res Int 2013, 2013:346762.
Fiorentino F., Caiazzo F., Napolitano S., Spizzichino L., Bono S., Sessa M., 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.
Firth H.V. 22q11.2 Duplication. GeneReviews™ 2009, [Internet], University of Washington, Seattle (WA), Seattle. R.A. Pagon, M.P. Adam, T.D. Bird, C.R. Dolan, C.T. Fong, K. Stephens (Eds.).
Girirajan S., Rosenfeld J.A., Coe B.P., Parikh S., Friedman N., et al. Phenotypic heterogeneity of genomic disorders and rare copy-number variants. NEngl J Med 2012, 367:1321-1331.
Haldeman-Englert C., Jewett T. 1q21.1 Microdeletion. GeneReviews™ 2011, [Internet], University of Washington, Seattle (WA), Seattle. R.A. Pagon, M.P. Adam, T.D. Bird, C.R. Dolan, C.T. Fong, K. Stephens (Eds.).
Itsara A., Wu H., Smith J.D., Nickerson D.A., Romieu I., London S.J., et al. De novo rates and selection of large copy number variation. Genome Res 2010, 20:1469-1481.
Lichtenbelt K.D., Knoers N.V., Schuring-Blom G.H. From karyotyping to array-CGH in prenatal diagnosis. Cytogen Gen Res 2011, 135:241-250.
Lundin J., Söderhäll C., Lundén L., Hammarsjö A., White I., Schoumans J., et al. 22q11.2 Microduplication in two patients with bladder exstrophy and hearing impairment. Eur J Med Genet 2010, 53:61-65.
Mefford H.C., Clauin S., Sharp A.J., Moller R.S., Ullmann R., Kapur R., et al. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet 2007, 81:1057-1069.
Miller D.T., Nasir R., Sobeih M.M., Shen Y., Wu B.L., Hanson E. 16p11.2 Microdeletion. GeneReviews™ 2011, [Internet], University of Washington, Seattle (WA), Seattle. R.A. Pagon, M.P. Adam, T.D. Bird, C.R. Dolan, C.T. Fong, K. Stephens (Eds.).
Moreno-De-Luca D., Mulle J.G., Kaminsky E.B., Sanders S.J., et al. Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet 2010, 87:618-630. SGENE Consortium, Simons Simplex Collection Genetics ConsortiumSimons Simplex Collection Genetics Consortium.
Portnoï M.F. Microduplication 22q11.2: a new chromosomal syndrome. Eur J Med Genet 2009, 52:88-93.
Rooryck C., Toutain J., Cailley D., Bouron J., Horovitz J., Lacombe D., et al. Prenatal diagnosis using array-CGH: a French experience. Eur J Med Genet 2013, 56:341-345.
Rosenfeld J.A., Coe B.P., Eichler E.E., Cuckle H., Shaffer L.G. Estimates of penetrance for recurrent pathogenic copy-number variations. Genet Med 2013, 15:478-481.
Schaffer L.G., Dabell M.P., Rosenfeld J.A., Neill N.J., Ballif B.C., Coppinger J., et al. Referral patterns for microarray testing in prenatal diagnosis. Prenat Diagn 2012, 32:611.
Toriello H.V. Thrombocytopenia absent radius syndrome. GeneReviews™ 2012, [Internet], University of Washington, Seattle (WA), Seattle. R.A. Pagon, M.P. Adam, T.D. Bird, C.R. Dolan, C.T. Fong, K. Stephens (Eds.).
Tyreman M., Abbott K.M., Willatt L.R., Nash R., Lees C., Whittaker J., et al. High resolution array analysis: diagnosing pregnancies with abnormal ultrasound findings. JMed Genet 2009, 46:531-541.
Ulinski T., Lescure S., Beaufils S., Guigonis V., Decramer S., Morin D., Clauin S., Deschênes G., et al. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. JAm Soc Nephrol 2006, 17:497-503.
Valduga M., Philippe C., Bach Segura P.B., Thiebauheorges O., Miton A., Beri M., et al. Aretrospective study by oligonucleotide array-CGH in 50 fetuses with multiple malformations. Prenat Diagn 2010, 30:333-341.
Vetro A., Bouman K., Hastings R., McMullan D.J., Vermeesch J.R., Miller K., et al. The introduction of arrays in prenatal diagnosis: a special challenge. Hum Mutat 2012, 33:923-929.
Wapner R.J., Martin C.L., Levy B., Ballif B.C., Eng C.M., Zachary J.M., et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. New Eng J Med 2012, 367:2175-2184.
Wat M.J., Veenma D., Hogue J., Holder A.M., Yu Z., Wat J.J., et al. Genomic alterations that contribute to the development of isolated and non-isolated congenital diaphragmatic hernia. JMed Genet 2011, 48:299-307.
