Analysis of tissue from products of conception and perinatal losses using QF-PCR and microarray: A three-year retrospective study resulting in an efficient protocol

• Published in: European journal of medical genetics 2016-08, Vol.59 (8), p.417-424
• Main Authors: Wou, K, Hyun, Y, Chitayat, D, Vlasschaert, M, Chong, K, Wasim, S, Keating, S, Shannon, P, Kolomietz, E
• Format: Article
• Language: English
• Subjects: Adult; Array CGH; Comparative Genomic Hybridization; Diagnostic yield; Female; Gestational Age; Humans; Male; Maternal Age; Medical Education; Middle Aged; Oligonucleotide Array Sequence Analysis - methods; Oligonucleotide Array Sequence Analysis - standards; Perinatal tissue; Polymerase Chain Reaction - methods; Polymerase Chain Reaction - standards; Pregnancy; Prenatal Diagnosis - methods; Prenatal Diagnosis - standards; QF-PCR; Retrospective Studies; Workflow; Young Adult
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2016.05.011

Abstract Objective To evaluate the performance of a laboratory protocol for direct genetic analysis performed on tissues obtained from miscarriages, stillbirth and postnatal death. Methods Samples were collected between July 1st, 2011 and June 30th, 2014. QF-PCR analysis was the initial test followed by aCGH analysis performed on the normal QF-PCR specimens. Results Of the 1195 submitted specimens, a total of 1071 samples were confirmed as true fetal. The failure rate was 1.4%. Of those, 30.8% yielded abnormal results. Of the latter, 57.6% had abnormal QF-PCR and 42.4% had abnormal microarray result. Autosomal trisomies were detected in 61.2%, triploidy in 7.6%, monosomy X in 9.1%, sex-chromosome aneuploidy (apart from monosomy X) in 1.5%, molar pregnancies in 5.8% and copy number variants in 14.2% including microdeletions/microduplications and cryptic unbalanced rearrangements. The highest diagnostic yield was observed in the 1st trimester specimens at 67.6%. We confirmed that maternal age correlates with the likelihood of autosomal trisomies but not with triploidy, sex chromosome aneuploidies, molar pregnancy, or CNVs. Conclusion An efficient laboratory protocol, based on QF-PCR and aCGH of uncultured cells has replaced standard cytogenetic analysis in testing of tissue from all pregnancy losses in our center and resulted in reduced test failure rate and increased diagnostic yield.