Overview of the clinical aspects of the fetuses with CNVs of unclear clinical significance.

<p>AF: amniotic fluid; CM: cisterna magna; CV: chorionic villi; DS: Down syndrome screening; FU: follow up; Gest: Gestation; IUGR: intrauterine growth restriction; N: not DS +ve or not mentioned; NT: nuchal translucency; SVC: superior vena cava; TGA: transposition of great arteries; TOF: Tetralogy of Fallot; TOP: termination of pregnancy; USS: ultrasound; Y: yes; +ve: positive.</p

Identical complex chromosomal rearrangements in chromosome 15 found in 2 prenatal samples with different karyotypes and phenotypes.

<p>Sample A karyotype is 46,XY,15q+ dn (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087988#pone-0087988-t003" target="_blank">Table 3</a>, 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.</p

Clinically significant CNVs other than common aneuploidies detected in the first-tier test study which were not detected by karyotyping.

<p>AF: amniotic fluid; ASD: atrial septal defect; CV: chorionic villi; DCDA: dichorionic diamniotic; DS: Down syndrome screening; FB: fetal blood; Gest: Gestation; IUGR: intrauterine growth restriction; PPROM: preterm premature rupture of membranes; TOP: termination of pregnancy; USS: ultrasound scan findings; w: weeks; +ve: positive.</p

Clinically significant CNVs detected in the first-tier test study.

<p>DS: Down syndrome screening; USS abn: ultrasound abnormality;</p><p>*percentage of clinical significant CNV found in the indication category.</p

Clinically significant CNVs other than common aneuploidies detected in the first-tier test study with additional information provided by aCGH over karyotyping.

<p>AF: amniotic fluid; ASD: atrial septal defect; CV: chorionic villi; DCDA: dichorionic diamniotic; DS: Down syndrome screening; FB: fetal blood; Gest: Gestation; IUGR: intrauterine growth restriction; PPROM: preterm premature rupture of membranes; TOP: termination of pregnancy; USS: ultrasound scan findings; w: weeks; +ve: positive.</p

Clinically significant CNVs other than common aneuploidies detected in the first-tier test study with abnormalities detected by both aCGH and karyotyping.

<p>AF: amniotic fluid; ASD: atrial septal defect; CV: chorionic villi; DCDA: dichorionic diamniotic; DS: Down syndrome screening; FB: fetal blood; Gest: Gestation; IUGR: intrauterine growth restriction; PPROM: preterm premature rupture of membranes; TOP: termination of pregnancy; USS: ultrasound scan findings; w: weeks; +ve: positive.</p

Proposed workflow for replacing karyotyping with aCGH in prenatal testing in Hong Kong.

<p>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.</p

Common benign CNVs found in Hong Kong.

<p>Kb: Kilobase.</p

Management recommendations for clinically significant CNVs and recommendation according to the level of evidence.

<p>Abbreviations: MCA = Multiple Congenital Anomalies; DD = Developmental Delay; ASD = Autism Spectrum Disorders; Dys = Dysmorphism; UCS = Uncertain Clinical Significance.</p><p>Abbreviations: S = Surveillance; R =  specialist Referral/assessment; D = Diagnostic testing; P = medical/surgical Procedure; M = Medication administration; L = Lifestyle recommendation; O = Other interventions.</p><p>* = pathogenic CNVs, ∧ = likely pathogenic CNVs.</p><p>N = not tested; Mat  =  maternal inheritance; Pat  =  paternal inheritance.</p><p>Management recommendations for clinically significant CNVs and recommendation according to the level of evidence.</p

CNVs type in patients with clinically significant CNVs and patients with CNVs of unknown clinical significance.

<p>CNVs type in patients with clinically significant CNVs and patients with CNVs of unknown clinical significance.</p