2008 Barcelona - European Society of Human Genetics

Prenental diagnostics
The Consortium has published best practice guidelines for PGD and
PGS and recently, a joint report with the European Society for Human
Genetics (ESHG) broadly examining the interface between genetics
and assisted reproductive technology . To further improve preimplantation
testing, studies are ongoing to investigate PGD laboratory accreditation,
appropriate external quality assessment, EQAS (multicentric
evaluation of captured FISH images from single embryonic nuclei) and
measures to facilitate real-time reporting of misdiagnoses and development
of preventative action to reduce the risk of recurrence . Survey
data regarding misdiagnosis, EQAS and confirmation of diagnosis on
embryos will be shared .
P03.27
Pre-implantation Genetic Diagnosis (PGD) for Genetic and
metabolic Disorders-the saudi Experience
A. I. Al-Aqeel1 , W. Quabashi2 , S. Coskun2 ;
1Riyadh Military Hospital/ King Faisal Specialist Hospital, Riyadh, Saudi Arabia,
2King Faisal Specialist Hospital, Riyadh, Saudi Arabia.
Saudi Arabian culture is highly consanguineous, with the first cousin
marriages accounting for 60-70% of all marriages. Given the difficulties
in management of genetic disorders, reproductive option for families
affected with genetic diseases in Saudi Arabia is often limited to
PGD which is permissible under the law and religion whereas prenatal
diagnosis with the intent of termination of pregnancy is neither widely
practiced nor socially accepted, although it is accepted under certain
conditions .
KFSH&RC has been offering PGD for monogenic and chromosomal
disorders, since 2001 . A total of 45 pregnancies initiated . Of which, 25
healthy babies were born, 13 pregnancies are ongoing and 7 pregnancies
were either biochemical or ended up with abortion .
In all these families PGD was undertaken using fluorescent PCR (F-
PCR) and/or nested PCR with sequencing on a single cell, or Multiple
Displacement Modification (MDA) to amplify the whole genome from
a single cell . A singleton pregnancy ensure after transfer of one heterozygous
and one/or normal embryo and prenatal diagnosis by CVS
confirmed a normal pregnancy. This is the first report of successful
PGD in different genetic disorders in Saudi Arabia, and the Muslim
world .
P03.28
Preimplantation Genetic Haplotyping for Duchenne/Becker
muscular dystrophy-birth of first male babies
P. J. Renwick, J. Trussler, A. Lashwood, P. Braude, C. Ogilvie;
PGD Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, United
Kingdom.
Preimplantation Genetic Diagnosis for sex-linked disorders undertaken
by sexing embryos is contentious as approximately 50% of the male
embryos discarded will be free of the mutation . Direct diagnosis of
dystrophin mutations is technically challenging due to heterogeneous
mutations and recombination hotspots . Since January 2006, we have
offered an alternative approach for Duchenne/Becker muscular dystrophy
(D/BMD) using Preimplantation Genetic Haplotyping (PGH) .
The first 10 cases (9 DMD + 1 BMD) are presented with follow-up to
February 2008 . In this cohort, 7 of the carrier females had different
exonic deletions, whilst 3 had different point/micro mutations, including
a germline mosaic . 15 microsatellite markers spanning the gene
were used, alongside 5 Y-chromosome markers to detect possible sex
chromosome aneuploidy .
57 embryos were biopsied with 50 diagnosed (88%) and 32 (56%)
suitable for transfer. The multiple displacement amplification (MDA)
used in PGH had a significantly lower (pG) . Albumin rate in
the amniotic fluid was reduced compared to controls, whereas alpha1
and beta protein fractions were increased .
Discussion - Conclusion
The c.543G>A mutation is the second sequence modification identified
so far in the AFP gene, responsible for its complete deficiency. Electrophoresis
results suggest that deficiency may modify protein fraction
repartition, particularly albumin, alpha1 and beta fractions suggesting
complex molecular mechanisms of compensation . Studies on other
families with AFP deficiency are necessary to confirm this observation
.
P03.30
the evaluation of chromosomal abnormalities diagnosed
prenataly in cluj-Napoca,Romania
M. S. Militaru, R. A. Popp, A. Trifa, M. Militaru, F. Stamatian;
University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Prenatal diagnosis for chromosomal disorders is performed routinely in
populations since most of these disorders have severe consequences
such as major malformations and mental retardation .Since advanced
technologies in rapid diagnostic tests have been developed to detect
common trisomies prenataly it is essential that each laboratory should
evaluate their own prenatal diagnosis profile.In this study we aimed
to investigate the type and proportion of chromosomal abnormalities
detected in cytogenetic studies prenataly and referral indications in
684 pregnant cases in Cluj-Napoca,Romania between the period of
2002-2007 .The overal chromosomal abnormality rate was found to be
49/684(7,76%) .The cytogenetic analysis with GTG banding of amniotic
fluid cells revelead:trisomy 21(12 cases),trisomy 18(7 cases),monosomy
X(6 cases),trisomy 16(1 case),trisomy 8(1 case),trisomy 15(1
case),robertsonian translocations(2 cases),Klinefelter syndrome(3
cases),autosomal deletions(3 cases),autosomal monosomy(2
cases),poliploidy(3 cases),chromosome marker(6 cases),trisomy X(1
case),Fra 5q31(1 case) .Careful genetic counseling by expert geneticists
regarding the patients indications is essential for determining the
cost-effective prenatal diagnostic test for each patient .
P03.31
Prenatal expression of Baraitser-Winter syndrome
G. Morin 1 , R. Goubet 1 , E. Gailly 1 , M. Mathieu 1 , B. Delaby 2 , S. Lanta 2 , P. Naepels
2 , A. Verloes 3 , J. Gondry 2 ;
1 Unité de Génétique Clinique, Amiens, France, 2 Centre de Diagnostic Prénatal,
Amiens, France, 3 Département de Génétique - Hôpital Robert Debré, Paris,
France.
Baraitser-Winter syndrome was first reported by these two authors in
1988 in a brother and a sister, and a girl unrelated to the two others .
The three patients had iris coloboma, hypertelorism, ptosis, mental re-
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