Figure 1.
A schematic diagram showing the indications for recruitment to the study and CNVs detected in the evaluation study.
The samples were subjected to first-tier test and ‘further-test’, with the clinical indications of testing and findings stated. aCGH, array CGH; CNVs, copy number variants; n, number of samples; DS +ve, Down syndrome screening positive; USS abn, ultrasound abnormality; Anxiety: maternal anxiety. Details on the clinically significant CNVs and CNVs of uncertain clinical significance are listed in Tables 1, 2, 3, 4, 5, 6.
Table 1.
Clinically significant CNVs detected in the first-tier test study.
Table 2.
Clinically significant CNVs other than common aneuploidies detected in the first-tier test study which were not detected by karyotyping.
Table 3.
Clinically significant CNVs other than common aneuploidies detected in the first-tier test study with additional information provided by aCGH over karyotyping.
Table 4.
Clinically significant CNVs other than common aneuploidies detected in the first-tier test study with abnormalities detected by both aCGH and karyotyping.
Table 5.
Overview of the clinical aspects of the fetuses with clinically significant CNVs detected in the further-test study with normal karyotype.
Table 6.
Overview of the clinical aspects of the fetuses with CNVs of unclear clinical significance.
Table 7.
Common benign CNVs found in Hong Kong.
Figure 2.
Identical complex chromosomal rearrangements in chromosome 15 found in 2 prenatal samples with different karyotypes and phenotypes.
Sample A karyotype is 46,XY,15q+ dn (Table 3, Case no. 8); Sample B karyotype is 47,XX,+mar from characterization study. Each dot on the X-axis represents one oligonucleotide probe on the respective chromosome position. Two-copy gain is detected at 15q11.2q13.2 with minimum gain of 7.77 Mb. Single copy gain is detected at 15q13.2q13.3 with minimum gain of 1.3 Mb. No probe is located in the segment between the 2 regions of copy gains, therefore the exact number of copy gained is unknown in the segment. The genetic syndromes (red boxes) and genes (green boxes) in the region denoted by Signature Genomics Genoglyphix software are shown in the lower panel.
Figure 3.
Proposed workflow for replacing karyotyping with aCGH in prenatal testing in Hong Kong.
Pregnancies with Down syndrome screening positive without ultrasound abnormalities can be subjected to non-invasive prenatal testing; while pregnancies with Down syndrome screening positive in the presence of ultrasound abnormalities can be subjected to invasive test by QF-PCR to exclude common aneuploidy and maternal contamination, followed by aCGH as shown. aCGH, array CGH; DS+ve, Down syndrome screening positive; FISH, fluorescent in-situ hybridization; NIPT, non-invasive prenatal testing; QF-PCR, quantitative fluorescent-polymerase chain reaction for common aneuploidy detection.