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QF-PCR stand-alone prenatal diagnosis:
the initial London experience.
Caroline Mackie Ogilvie
Cytogenetics Department
Guy’s Hospital
London
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Guy’s QF-PCR data
2000 - 2007
Total samples tested: 23,311
CVS
6729 (28.9%)
AF
16582 (71.1%)
97% of samples receive a result within one
working day
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Should we karyotype pregnancies at
risk of Down syndrome?
• 32,674 pregnant women having invasive PND in
London/South East
• 24,891 (76.2%) were referred for exclusion of Down
syndrome
• others at risk of single gene disorders or complex
chromosome abnormalities
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• 24,891 pregnancies referred for exclusion of T21
• 118 sex chromosome abnormalities
• 153 other abnormalities
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Abnormal karyotypes:
Good prognosis:
– balanced rearrangements
– variant regions
Uncertain prognosis:
– small marker chromosomes
– mosaic anomalies
Poor prognosis
– non-mosaic genomic imbalance
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Trisomy risk referrals
n=24,891
140
120
100
n
80
60
40
20
0
Sex
GP
UP
PP
0.47%
0.39%
0.15%
0.07%
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Poor Prognosis n = 18
 1 liveborn (10q del) minor facial dysmorphism
but normal development at 20 months
 2 miscarried
 4 outcome unknown, of which 1 = T16,
2 = 46,XX,del(18), 1=46,XX,add(9)
 11 TOP (61%)
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Advantages of QF-PCR stand-alone
testing
• uncertain or harmless karyotypes not detected,
reducing anxiety and follow-up studies
• no residual anxiety while waiting for karyotype
results
• better use of resources
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New service May 2007
All abnormal QF-PCR results followed up by
karyotype analysis
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Criteria for karyotyping
Clinical indication, viz:
• structural abnormality on U/S
• 2 or more soft markers for trisomy 21
• nuchal measurement >3mm at below 14 weeks
gestation
• nuchals measurement >6mm for gestations >= 14 weeks
• family history of chromosome rearrangement
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Data from 3 London labs
01/05/2007 – 30/11/2007
Consortium samples only
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AF samples
n=1502
QF-PCR +
karyotype
21%
QF-PCR
79%
CVS samples
n=628
QF-PCR +
karyotype
45%
Karyotype
only
1%
QF-PCR
only
54%
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AF abnormals
n=122
Abnormals
not
detected by
QF-PCR
11%
QF-PCR
abnormals
89%
CVS abnormals
n=135
Abnormals
not
detected by
QF-PCR
15%
QF-PCR
abnormals
85%
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Abnormalities not detected by
QF-PCR
Detection rate in karyotyped AF
Detection rate in karyotyped CVS
3%
7%
No abnormal babies reported to date.
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Abnormalities not detected by
QF-PCR
One pregnancy:
• QF-PCR only at CVS
• ultrasound showed severe IUGR and abnormal placenta
at 26 weeks
• follow-up amnio: mos tetraploidy
• pregnancy terminated
• fetal blood showed normal karyotype
Tetraploid cell line probably confined to placenta leading to
placental insufficiency
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NT >3mm<4mm
“An alternative strategy whereby qf-PCR is the main method
of analysis and full karyotyping is reserved for those cases
with a minimum fetal NT thickness of 4 mm would require
full karyotyping in 10.1% of the cases, would identify 99.0%
of the significant abnormalities, and would cost 60% less
than full karyotyping for all.”
Chitty et al. (2006) BMJ 25;332(7539):452-5.
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NT >3mm<4mm
abnormality not
detected by QFPCR
3%
normal/trisomy
97%
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NT >3mm<4mm
2 abnormal karyotypes in this group
• 47,XY,+22
• 47,XX,+mar[19]/46,XX[28]
–
–
–
–
v small non-satellited marker, apparently all
heterochromatin
?CPM
follow-up amnio and parental bloods requested, but
not forthcoming
pregnancy terminated
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Collaborators
Guy’s
Kathy Mann
Zoe Docherty
NEL Regional Cyto Lab
(GOSH)
NWT Regional Cyto Lab
(KGC)
Jonathan Waters
Melissa Holloway
Sandra Edwards
Deborah Morrogh
Richard Ellis
Janine Burbridge
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