J A Rosenfeld1,2, M E Tucker3, L F Escobar3, N J Neill1,2, B S Torchia1, L D McDaniel1, R A Schultz1, K Chong4, D Chitayat4. 1. Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, WA, USA. 2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. 3. St. Vincent Hospital, Indianapolis, IN, USA. 4. The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Abstract
OBJECTIVES: To determine the frequency of clinically significant chromosomal abnormalities identified by chromosomal microarray in pregnancy losses at any gestational age and to compare microarray performance with that of traditional cytogenetic analysis when testing pregnancy losses. METHODS: Among 535 fetal demise specimens of any gestational age, clinical microarray-based comparative genomic hybridization (aCGH) was performed successfully on 515, and a subset of 107 specimens underwent additional single nucleotide polymorphism (SNP) analysis. RESULTS: Overall, clinically significant abnormalities were identified in 12.8% (64/499) of specimens referred with normal or unknown karyotypes. Detection rates were significantly higher with earlier gestational age. In the subset with normal karyotype, clinically significant abnormalities were identified in 6.9% (20/288). This detection rate did not vary significantly with gestational age, suggesting that, unlike aneuploidy, the contribution of submicroscopic chromosomal abnormalities to fetal demise does not vary with gestational age. In the 107 specimens that underwent aCGH and SNP analysis, seven cases (6.5%) had abnormalities of potential clinical significance detected by the SNP component, including female triploidy. aCGH failed to yield fetal results in 8.3%, which is an improvement over traditional cytogenetic analysis of fetal demise specimens. CONCLUSIONS: Both the provision of results in cases in which karyotype fails and the detection of abnormalities in the presence of a normal karyotype demonstrate the increased diagnostic utility of microarray in pregnancy loss. Thus, chromosomal microarray testing is a preferable, robust method of analyzing cases of pregnancy loss to better delineate possible genetic etiologies, regardless of gestational age.
OBJECTIVES: To determine the frequency of clinically significant chromosomal abnormalities identified by chromosomal microarray in pregnancy losses at any gestational age and to compare microarray performance with that of traditional cytogenetic analysis when testing pregnancy losses. METHODS: Among 535 fetal demise specimens of any gestational age, clinical microarray-based comparative genomic hybridization (aCGH) was performed successfully on 515, and a subset of 107 specimens underwent additional single nucleotide polymorphism (SNP) analysis. RESULTS: Overall, clinically significant abnormalities were identified in 12.8% (64/499) of specimens referred with normal or unknown karyotypes. Detection rates were significantly higher with earlier gestational age. In the subset with normal karyotype, clinically significant abnormalities were identified in 6.9% (20/288). This detection rate did not vary significantly with gestational age, suggesting that, unlike aneuploidy, the contribution of submicroscopic chromosomal abnormalities to fetal demise does not vary with gestational age. In the 107 specimens that underwent aCGH and SNP analysis, seven cases (6.5%) had abnormalities of potential clinical significance detected by the SNP component, including female triploidy. aCGH failed to yield fetal results in 8.3%, which is an improvement over traditional cytogenetic analysis of fetal demise specimens. CONCLUSIONS: Both the provision of results in cases in which karyotype fails and the detection of abnormalities in the presence of a normal karyotype demonstrate the increased diagnostic utility of microarray in pregnancy loss. Thus, chromosomal microarray testing is a preferable, robust method of analyzing cases of pregnancy loss to better delineate possible genetic etiologies, regardless of gestational age.
Authors: Aleena M Wojcieszek; Emily Shepherd; Philippa Middleton; Glenn Gardener; David A Ellwood; Elizabeth M McClure; Katherine J Gold; Teck Yee Khong; Robert M Silver; Jan Jaap Hm Erwich; Vicki Flenady Journal: Cochrane Database Syst Rev Date: 2018-04-30
Authors: Christine M Armour; Shelley Danielle Dougan; Jo-Ann Brock; Radha Chari; Bernie N Chodirker; Isabelle DeBie; Jane A Evans; William T Gibson; Elena Kolomietz; Tanya N Nelson; Frédérique Tihy; Mary Ann Thomas; Dimitri J Stavropoulos Journal: J Med Genet Date: 2018-03-01 Impact factor: 6.318
Authors: Chelsea Lowther; Marsha Speevak; Christine M Armour; Elaine S Goh; Gail E Graham; Chumei Li; Susan Zeesman; Malgorzata J M Nowaczyk; Lee-Anne Schultz; Antonella Morra; Rob Nicolson; Peter Bikangaga; Dawa Samdup; Mostafa Zaazou; Kerry Boyd; Jack H Jung; Victoria Siu; Manjulata Rajguru; Sharan Goobie; Mark A Tarnopolsky; Chitra Prasad; Paul T Dick; Asmaa S Hussain; Margreet Walinga; Renske G Reijenga; Matthew Gazzellone; Anath C Lionel; Christian R Marshall; Stephen W Scherer; Dimitri J Stavropoulos; Elizabeth McCready; Anne S Bassett Journal: Genet Med Date: 2016-05-19 Impact factor: 8.822