pgd for single disorders pgd for single gene disorders an update from edinburgh sally morton,...
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PGD for single PGD for single gene disorders disorders
An update from Edinburgh
Sally Morton, Genetic Counsellor
23 November 2010
Topics covered
Principle of PGD and haplotyping
Criteria to receive treatment in Edinburgh
Pilot study update
What should couples expect?
Which family samples required?
IVF
ICSI
Human preimplantationDevelopmentDevelopment day 0-2
Fertilised egg 2 cell embryo 4 cell embryo
Cleavage stage Biopsy
Placement of CF markers with respect to p.Phe508del
MS3MS14.6Mb 0.7 Mb 2.6 Mb
0.4Mb
MS6
MS19
CFTR
IVS8CA
IVS1CA
D7S2847
D7S643
D7S480
D7S650
D7S2460D7S2502
D7S2554
p.Phe508
11.3Kb
69.4 KbCFSTR10.3 Mb
1.5 Mb
3.6 Mb
3.7Mb
3.7Mb
0.7Mb
D7S4861.2 Mb
1.7Mb
2.7 Mb
CFTR
Results from D7S643 marker
Mother
Father
Affected child
Embryo
PGD assays that are set up
CF
SMA
HD or 50% risk of HD
FraX
ADRP
PGD assays being set up next
DMD
Myotonic dystrophy
Beta thalassemia
VHL
For new conditions, allow up to one year for assay to be set up
Criteria to receive funded PGD in Edinburgh
Known genetic riskNo unaffected child* with residencyFemale age<40Anti mullerian hormone (AMH) > or = 5Adequate follicle count Female BMI<30Both partners must have “right of residency”
* If have unaffected child, can still have treatment but it would have to self-fund
Levels of fertility with respect to AMH levels (pmol/L)
** associated with polycystic ovary syndrome or granulosa tumour
0 2.2 15.7 28.6 48.5
Very low
Low Satisfactory Optimal High *
Source of PGD referrals24 couples referred Aug 09 - Nov 10
0
2
4
6
8
10
12
Edinburgh Glasgow Falkirk/Stirling Dundee Aberdeen
Referred by…
Genetics
Obsn
Self
For which condition?
0123456789
10
CF HD DMD FraX Myot B thal VHL ALD Ecad ADRP Haem A
Age of female partner
0
2
4
6
8
10
12
20-24 25-29 30-34 35-39
Pilot study update
Three CF couples have completed a treatment cycle.
One couple having second cycle
One couple having second thaw cycle
One couple delivered 14 Nov 2010!
Looking forward
3 couples starting treatment Dec 2010 (FraX, HD, CF)
4 couples ready to start early in New Year (50% risk HD, HD, CF, ADRP)
New referral form (Nov 10)
What to expect?
2 w e ek s t il p re g te st
O n e e m bryo re p la c ed
E m bryo b io p sy & tes ting
IC S I cyc le in clse ve ra l s c a ns
S che d u le sta rt m o n th
3rd appt at ERIIV F nu rse
S e m en a na lys is
2nd appt at ERIIV F c o nsu lta n t,
n u rse & S MO v aria n s can
1st appt at W GHM P /S M
A M H a n d B M I m e as u redR e fe r to IV F te am
D isc usse d a t P G D te am m tg
R e fe rra l re c 'd u s ing n e w re fe rra l fo rme n c l re p o rts , pe d ig re e , pa rtne r d e ta ils, A M H
What samples are needed to offer PGD haplotyping?
Need a ‘triplet of samples’
Dominant condition = affected individual and their parents. Partner also helpful.
X-linked condition = couple and affected child or affected parent
Recessive condition = couple and affected child (or both set of parents of couple if no affected child in family)
Thank you
Enquiries welcome
Tel: 0131 537 1116
6-weekly PGD team meeting
Any questions?