2008 Barcelona - European Society of Human Genetics

Prenental diagnostics
However, universal fetal markers would allow its diffusion to a wider
number of applications and clinical cases .
More recently epigenetics has shown encouraging results toward this
goal . Our aim was to investigate the methylation status of selected
promoter regions of chromosome 18 genes in maternal blood and placenta
samples .
A total of 36 genes on chromosome 18 were selected after database
search for sequences with different expression patterns in placenta
and blood . Primers were designed to analyse as much CpG islands
as possible in 102 promoter sequences for the presence of different
methylation patterns in fetal tissue (CVS) and whole blood (WB) . Digestion
with 4 methylation-dependent restriction enzymes was carried
out on extracted DNA samples prior to PCR amplification to investigate
the presence of differentially methylated sequences .
Two promoter regions were found hypermethylated in CVS and hypomethylated
in WB . One more gene promoter was found with the
opposite pattern being hypomethylated in CVS and hypermethylated
in WB .
In this study we found three genes on chromosome 18 with apparently
differentially methylated promoters between placenta and whole blood .
We are in the process of developing assays to detect the placental
form in maternal plasma. These preliminary results confirm the effectiveness
of an epigenetic approach to find biomarkers for the analysis
of free fetal DNA in maternal plasma .
P03.42
Screening and nuchal translucency in first and second
trimester: efficiency in the selection of pregnant women at risk
of chromosomopathies
A. Sánchez 1,2 , N. Clusellas 1 , C. Morales 1 , J. Bruguera 3 , I. Mademont 4 , R. Queralt
1 , V. Borobio 5 , A. Borrell 5,2 , E. Casals 1 , A. Soler 1,2 ;
1 Servei de Bioquímica i Genètica Molecular, Hospital Clínic, Barcelona, Spain,
2 IDIBAPS, Barcelona, Spain, 3 Fundació Clínic per a la Recerca Biomèdica,
Barcelona, Spain, 4 CIBERER, Barcelona, Spain, 5 Servei de Medicina Maternofetal,
Hospital Clínic, Barcelona, Spain.
First trimester screening for trisomy 21 is provided by a combination
of maternal age, fetal nuchal translucency and maternal serum free
β-hCG and PAPP-A concentration between 11-13 weeks of gestation.
The detection rate of trisomy 21 is 90% with a false positive rate of
5% which is superior to the 65% achieved by second-trimester serum
biochemistry . We report a series of 5285 gestations that were referred
to maternal-fetal medicine department between 2003 and 2007 who
underwent an invasive prenatal diagnosis . A total of 1986 samples
were CVS and 3299 were amniotic fluid samples. In first trimester the
12,7% of the samples were referred due to positive combined screening
(+SC) and the 13,7% due to increased nuchal translucency (INT)
as unique abnormal parameter . In second trimester the 39% of the
samples were referred for positive second trimester screening and
the 2,5% for increased nuchal translucency . In the second trimester
samples the 1,4% of +SC and the 9,3% of INT showed a chromosomopathy.
In the first trimester samples the 12% of +SC and 25% of
INT presented chromosomal abnormalities. In first trimester we must
perform 5,5 invasive procedures to find a chromosomopathy in group
of patients with the reported indications, whereas in the second trimester
53 invasive procedures are needed to detect a chromosomal
abnormality. These results emphasise the higher efficiency of first trimester
screening over the second besides the medical advantages of
an early diagnosis .
P03.43
First-trimester screening protocols and their impact in
cytogenetic counselling
C. Cotarelo-Pérez, R. Oancea, M. Fenollar-Cortés, M. Ortega-de-Heredia, J.
Montalvo-Montes, M. Lautre-Ecenarro;
Hospital Clínico San Carlos, Madrid, Spain.
In the last few years, we have referred an increase of diagnosis prenatal
(DP) due to advanced maternal age and more knowledge of the
general population about possible diagnosis methods . The assumption
of first-trimester screening protocols (ultrasound and biochemistry
methods) has allowed to generalize the DP to all pregnant women, independently
of maternal age . We present our results after seven years
with the combined test and its impact on the cytogenetics prenatal
diagnosis . We analyzed data from 5743 singleton pregnancies under-
going prenatal genetic counselling from the area 7 of Madrid . 4930
woman where testing by first-trimester combined biochemistry and
ultrasound nuchal translucency screening . In 1998, 13% of the pregnant
women renounced amniocentesis opposite a 50% of renounces
in 2007. The implementing of first-trimester screening has reduced the
number of amniocentesis and made an individual better earlier genetic
counselling .
P03.44
Prenatal Diagnosis of a fetus with 44 chromosomes and
homozygous Robertsonian translocations (14;21)
S. Sodia, W. Emberger, H. Zierler, M. Speicher;
Medical University Graz, Graz, Austria.
We report the rare finding of a human fetus with 44 chromosomes
due to homozygous Robertsonian translocations (14;21) . The related
parents, born in Turkey, were referred to our Genetic Department for
genetic counselling at 16th weeks of gestation due to advanced maternal
age . Amniocentesis was performed and the analysis of amniotic
fluid cells revealed 44 chromosomes with a homozygous Robertsonian
translocations (14;21):
44,XX,der(14;21)(q10;q10),der(14,21)(q10;q10) . At the time of amniocentesis
there were no pathological ultrasound findings. Karyotyping
of the consanguineous parents showed in each case the same heterozygous
Robertsonian translocations(14;21) . Family history revealed
that the translocation has segregated through at least four generations
. Because UPD testing should be considered in fetuses carrying a
balanced Robertsonian translocation involving chromosomes 14 or 15,
we excluded in our case UPD 14 . Although Robertsonian translocations
are common chromosomal rearrangements, homozygous carriers
are rare . Previously reported single case reports showed no evidence
for an increased risk for malformations or dysmorphic features in carriers
of homozygous Robertsonian translocations .
P03.45
Prenatally detected mosaicism - 46,X,idic(Y)(q11.2)/45,X. A case
report
P. Tammur, K. Kuuse, P. Ilisson, M. Sitska;
Department of Genetics, Tartu, Estonia.
Isodicentric Y chromosomes are inherently unstable and may be lost
during mitosis resulting in mosaicism, generally including a 45,X cell
line . Clinical presentations in patients with mosaicism for a structurally
abnormal Y chromosome can range from classical Turner phenotype
through mixed gonadal dysgenesis to phenotypically normal males .
The variability in sexual phenotype is thought to be related to the tissue
distribution, to the proportion of each cell line and to the location of the
breakpoints . However, prenatal diagnosis of mosaic 46,X,idic(Y)/45,X
is rare, and poses a serious dilemma concerning the prognosis related
to the fetal stature, sexual differentiation and the risk development of
gonadoblastoma .
In our case amniocentesis was performed to a 33-year-old women
because of positive serum screening on the 15 week of pregnancy .
Cultured amniocytes from two different culture flasks revealed mosaic
karyotype 46,X,+mar[36]/45,X[14] . For detecting the origin of marker
chromosome, fluorescence in situ hybridisation (FISH) was performed
1)with X and Y centromeric probes (AneuVysion, X, Y-alpha satellite
probe) and 2) XYpter subtelomere specific probe (Cytocell). FISH
analysis revealed that the marker chromosome was isodicentric Y
chromosome with two short arms and a small portion of the long arm:
46,X,idic(Y)(q11 .2)[41]/45,X[44] . After further genetic counselling, the
parents opted for termination of the pregnancy . Postmortem examination
revealed male fetus with microanomalies and no major abnormalities
. Cytogenetic analysis of the placenta showed mosaicism in a different
degree 46,X,idic(Y)(q11 .2)[46]/45,X[4] and mosaicism was also
found in fetal tissues .
P03.46
is informed choice in the context of prenatal testing a
universally held value?
A. van den Heuvel1 , E. Dormandy1 , L. Chitty2 , T. M. Marteau1 ;
1 2 King’s College London, Institute of Psychiatry, London, United Kingdom, Institute
of Child Health and UCLH, London, United Kingdom.
Background: Informed choice is central to prenatal testing and endorsed
by many national and international guidelines for prenatal