Genomic Characterization of Prenatally Detected Chromosomal Structural Abnormalities Using Oligonucleotide Array Comparative Genomic Hybridization

• Type of Material: Article
• Authors: Peining Li, Yale University; Pawei Pomianowski, Yale University; Miriam S. DiMaio, Yale University; Joanne R. Florio, Yale University; Michael Rossi, Emory University; Bixia Xiang, City of Hope; Fang Xu, Yale University; Hui Yang, Yale University; Qian Geng, Shenzhen Maternity and Child Healthcare Hospital; Jiansheng Xie, Shenzhen Maternity and Child Healthcare Hospital; Maurice J. Mahoney, Yale University
• Language: English
• Date: 2011-07-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Wiley-Liss, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/ajmg.a.34043
• Title of Journal or Parent Work: American Journal of Medical Genetics Part A
• ISSN: 1552-4825
• Volume: 155A
• Issue: 7
• Start Page: 1605
• End Page: 1615
• Grant/Funding Information: NIH training grant 5T32GM008753-09 to MRR supported part of this work.
• Keywords: PHENOTYPE; DIAGNOSIS; MICROARRAY ANALYSIS; genomic imbalances; chromosomal structural abnormalities; array comparative genomic hybridization (aCGH); Science & Technology; MECHANISMS; DELETIONS; prenatal diagnosis; CGH; MENTAL-RETARDATION; Life Sciences & Biomedicine; REGIONS; Genetics & Heredity; GIRL
• Research Categories: Psychology, Developmental; Biology, Genetics

Abstract

Detection of chromosomal structural abnormalities using conventional cytogenetic methods poses a challenge for prenatal genetic counseling due to unpredictable clinical outcomes and risk of recurrence. Of the 1,726 prenatal cases in a 3-year period, we performed oligonucleotide array comparative genomic hybridization (aCGH) analysis on 11 cases detected with various structural chromosomal abnormalities. In nine cases, genomic aberrations and gene contents involving a 3p distal deletion, a marker chromosome from chromosome 4, a derivative chromosome 5 from a 5p/7q translocation, a de novo distal 6q deletion, a recombinant chromosome 8 comprised of an 8p duplication and an 8q deletion, an extra derivative chromosome 9 from an 8p/9q translocation, mosaicism for chromosome 12q with added material of initially unknown origin, an unbalanced 13q/15q rearrangement, and a distal 18q duplication and deletion were delineated. An absence of pathogenic copy number changes was noted in one case with a de novo 11q/14q translocation and in another with a familial insertion of 21q into a 19q. Genomic characterization of the structural abnormalities aided in the prediction of clinical outcomes. These results demonstrated the value of aCGH analysis in prenatal cases with subtle or complex chromosomal rearrangements. Furthermore, a retrospective analysis of clinical indications of our prenatal cases showed that approximately 20% of them had abnormal ultrasound findings and should be considered as high risk pregnancies for a combined chromosome and aCGH analysis.