title: Implementation of high resolution whole genome array CGH in the prenatal clinical setting: advantages, challenges, and review of the literature.
abstract: Array Comparative Genomic Hybridization analysis is replacing postnatal chromosomal analysis in cases of intellectual disabilities, and it has been postulated that it might also become the first-tier test in prenatal diagnosis. In this study, array CGH was applied in 64 prenatal samples with whole genome oligonucleotide arrays (BlueGnome, Ltd.) on DNA extracted from chorionic villi, amniotic fluid, foetal blood, and skin samples. Results were confirmed with Fluorescence In Situ Hybridization or Real-Time PCR. Fifty-three cases had normal karyotype and abnormal ultrasound findings, and seven samples had balanced rearrangements, five of which also had ultrasound findings. The value of array CGH in the characterization of previously known aberrations in five samples is also presented. Seventeen out of 64 samples carried copy number alterations giving a detection rate of 26.5%. Ten of these represent benign or variables of unknown significance, giving a diagnostic capacity of the method to be 10.9%. If karyotype is performed the additional diagnostic capacity of the method is 5.1% (3/59). This study indicates the ability of array CGH to identify chromosomal abnormalities which cannot be detected during routine prenatal cytogenetic analysis, therefore increasing the overall detection rate. In addition a thorough review of the literature is presented.
authors.affiliation: Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
authors.forename: Paola
authors.initials: P
authors.lastname: Evangelidou
authors.forename: Angelos
authors.initials: A
authors.lastname: Alexandrou
authors.forename: Maria
authors.initials: M
authors.lastname: Moutafi
authors.forename: Marios
authors.initials: M
authors.lastname: Ioannides
authors.forename: Pavlos
authors.initials: P
authors.lastname: Antoniou
authors.forename: George
authors.initials: G
authors.lastname: Koumbaris
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kallikas
authors.forename: Voula
authors.initials: V
authors.lastname: Velissariou
authors.forename: Carolina
authors.initials: C
authors.lastname: Sismani
authors.forename: Philippos C
authors.initials: PC
authors.lastname: Patsalis
mesh_terms: D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D011247:Pregnancy; D011296:Prenatal Diagnosis
references.citation: Eur J Hum Genet. 2004 Aug;12(8):647-53
references.pmid: 15162125
references.citation: BMC Genomics. 2005 Dec 13;6:180
references.pmid: 16351727
references.citation: J Med Genet. 2010 Sep;47(9):586-94
references.pmid: 20577003
references.citation: Hum Mutat. 2012 Jun;33(6):923-9
references.pmid: 22508381
references.citation: Prenat Diagn. 2009 Jan;29(1):29-39
references.pmid: 19012303
references.citation: Prenat Diagn. 2011 Mar;31(3):235-43
references.pmid: 21374637
references.citation: Genet Med. 2006 Nov;8(11):719-27
references.pmid: 17108764
references.citation: Lancet. 1966 Feb 19;1(7434):383-5
references.pmid: 4159775
references.citation: Ultrasound Obstet Gynecol. 2011 Jan;37(1):6-14
references.pmid: 20658510
references.citation: Acta Pathol Microbiol Scand. 1968;73(1):73-7
references.pmid: 5691288
references.citation: Am J Med Genet. 1997 May 16;70(2):179-87
references.pmid: 9128940
references.citation: Prenat Diagn. 2008 Sep;28(9):789-95
references.pmid: 18646242
references.citation: J Med Genet. 2009 Aug;46(8):531-41
references.pmid: 19451135
references.citation: Prenat Diagn. 2009 Dec;29(13):1213-7
references.pmid: 19862770
references.citation: Prenat Diagn. 2006 Apr;26(4):303-7
references.pmid: 16491515
references.citation: Cytogenet Cell Genet. 1978;22(1-6):352-6
references.pmid: 752501
references.citation: Prenat Diagn. 2010 Apr;30(4):333-41
references.pmid: 20155755
references.citation: Fetal Diagn Ther. 2009;25(2):277-84
references.pmid: 19521095
references.citation: J Med Genet. 2005 Feb;42(2):121-8
references.pmid: 15689449
references.citation: Cytogenet Genome Res. 2011;135(3-4):241-50
references.pmid: 22086062
references.citation: Genome Res. 2006 Dec;16(12):1566-74
references.pmid: 17122085
references.citation: Eur J Hum Genet. 2012 Feb;20(2):166-70
references.pmid: 21915152
references.citation: Prenat Diagn. 2008 Oct;28(10):943-9
references.pmid: 18792925
references.citation: Prenat Diagn. 2009 Dec;29(12):1156-66
references.pmid: 19795450
references.citation: Prenat Diagn. 2011 Dec;31(13):1270-82
references.pmid: 22034057
references.citation: Hum Mutat. 2012 Jun;33(6):906-15
references.pmid: 22415865
references.citation: Lancet. 2005 Jul 9-15;366(9480):97-8
references.pmid: 16005312
references.citation: N Engl J Med. 2012 Dec 6;367(23):2175-84
references.pmid: 23215555
references.citation: Hum Mutat. 2012 Jun;33(6):916-22
references.pmid: 22396320
references.citation: Mol Cytogenet. 2010 Nov 26;3:24
references.pmid: 21110858