Genomic characterization of prenatally detected chromosomal structural abnormalities using oligonucleotide array comparative genomic hybridization

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.

Design and validation of a pericentromeric BAC clone set aimed at improving diagnosis and phenotype prediction of supernumerary marker chromosomes

“…Among the non-acrocentric marker chromosomes collected in our series, the SMC characterization revealed breakpoints within pericentromeric noncritical regions in two cases [4,14-16,20,22,33,34], consistent with the observation that the corresponding patients (3 and 15) had normal phenotypes (Figures 2A–C and 3A–D, Additional file 2: Table S2). Notably, the association of sSMC(2) and sSMC(18) observed in patient 15 has not been previously reported.…”

Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature

“…7,17 For these reasons, CMA has become widely used in clinical diagnostics for postnatal and more recently, prenatal diagnosis. 4,6,10,17,21,22,26,27 Although CMA has been validated for the clinical diagnosis of copy number abnormalities in prenatal samples in a number of smaller studies, 21,22,[27][28][29][30][31][32][33][34] current recommendations by the American College of Obstetricians and Gynecologists (ACOG) and European Best Practice Guidelines do not yet include offering CMA to all patients undergoing invasive prenatal testing, 35,36 but ACOG has endorsed it as an appropriate adjunct test in prenatal cases with abnormal ultrasound findings and a normal karyotype. A large multicenter trial investigating the role of CMA in prenatal diagnosis is nearing completion in the USA, and it is anticipated that its results may direct future revision of these guidelines.…”

Molecular characterization of 39 de novosSMC: contribution to prognosis and genetic counselling, a prospective study

“…Array-CGH and SNP array are powerful tools for delineating chromosomal imbalances. However, there have been no large series reporting the application of this technology to sSMC in a postnatal (14)(15)(16)(17)(18)(19)(20)(21)(22) or prenatal context (23)(24)(25)(26)(27)(28)(29), or both (30,31). Genotype-phenotype correlations should be extended, and SNP array also offers the possibility to detect uniparental disomy (UPD), in particular, for sSMC derived from chromosome 6, 7, 11 and 20 (32,33).…”