2008 Barcelona - European Society of Human Genetics

Prenental diagnostics
tardation, large nasal root, and epicanthus . Two similar observations
with pericentric inversion of chromosome 2 were reported . In 1995, the
possibility of gyration abnormalities and trigonocephaly was noticed .
Due to the initial familial observation, an autosomal recessive mode of
inheritance was suggested .
We report the observation of a young boy, presenting with this condition
. His prenatal history was marked by hygroma colli with normal
karyotype, persisting along the pregnancy, associated from the second
trimester with renal dilatation and intestinal hyperechogenicity . At
birth, Noonan syndrome was first considered. PTPN11 analysis was
performed but negative . At the age of 4, due to suggestive dysmorphic
features, the diagnostic of Baraitser-Winter syndrome was made .
However the patient had no iris coloboma or gyration abnormality . We
discuss the similarities with Noonan syndrome, even during the prenatal
period .
P03.32
Prenatal detection and molecular characterisation of two
supernumerary marker chromosomes (smc) derivatives of
chromosome 22 in two unrelated patients.
S. Andreu 1 , M. Jodar 1 , G. Arnedo 1 , O. Villa 2,3 , B. Perez 4 , R. Villanueva 5 , N.
Kosyakova 6 , L. Pérez Jurado 2,3 , C. Fuster 7 , A. Escalona 1,7 ;
1 Analisis MDB. Lab Duran Bellido, Barcelona, Spain, 2 Unitat de Genètica.
Universitat Pompeu Fabra, Barcelona, Spain, 3 Center for Biomedical Research
on Rare Diseases (CIBERER), Barcelona, Spain, 4 Centre de Ginecologia i
Reproducció, Barcelona, Spain, 5 Centro Médico Augusta, Barcelona, Spain,
6 Institut für Humangenetik und Anthropologie, Jena, Germany, 7 Unitat de Biologia
Cel•lular i Genètica Mèdica. Facultat Medicina. Universitat Autònoma de
Barcelona, Barcelona, Spain.
SMC are ‘additional markers’ whose origin and composition cannot
be determined by conventional cytogenetics . Genetic counseling of
patients with SMC can be difficult, especially in prenatal testing, due
to the complexity in establishing a karyotype-phenotype correlation . In
fact, it has been estimated that about 37% of prenatal diagnosed SMC
are associated with an abnormal phenotype . We report two cases of
prenatal diagnosed SMC, detected by G-banding and completed by
C-banding and NOR-staining. In the first case, the marker was familial,
segregating from a mother with non-mosaic karyotype . In the second
case, the SMC was de novo and present in the 78% of cells . The following
FISH procedures were performed to confirm and specify the
material present in the marker chromosomes: locus-specific identifier,
24-colour FISH, CGH, chromosomal manual microdissection and reverse
FISH. These techniques identified both SMC as derivatives of
chromosome 22. In the first case, the inherited SMC was an iso(22p)
and the child was delivered successfully without phenotypic abnormalities
. In the second case, the SMC was a der(22)(q11 .2), resulting in a
partial trisomy of band 22q11 .2, which has been associated with Cateye
syndrome (CES) in the literature . In this case the pregnancy was
interrupted . It can be concluded with this study that familial markers
representing an iso(22p) can be correlated with a normal phenotype .
Also, this work proves the importance of the application of molecular
cytogenetic procedures to know the origin of de novo SMC, in order to
give accurate prenatal genetic counseling .
P03.33
cell-free DNA levels during labor at term and preterm deliveries
S. Rosenberger1 , S. Reisinger1 , E. Magnet2 , M. Bauer2 , A. Groselj-Strele3 , U.
Lang2 , B. Pertl1 ;
1 2 Medical University of Graz, Graz, Austria, Department of Obstetrics and Gynecology,
Graz, Austria, 3Center for medical research, Graz, Austria.
The aim was to evaluate the effect of uterine contractions on cell free
fetal-DNA (cff) and total DNA levels in maternal plasma during term
and preterm deliveries . Further we determined whether the cff- DNA
concentration from maternal plasma samples during deliveries at term
are different from those with preterm deliveries .
Maternal venous blood samples were collected during deliveries from
65 pregnant women with male fetuses . 46 pregnant women delivered
at term and 19 delivered preterm . Cff-DNA levels were analyzed by
quantitative real-time PCR using the SRY-assay and total DNA levels
were analyzed using the beta-Globin-assay . 148 pregnant women at
term without labor served as controls for women in labor at term . Preterm
samples (>27wks, 28-31wks, 32-36 wks, >36 wks) were matched
for gestational age to control samples without labor .
Cff-DNA levels in plasma samples from women during delivery at term
were statistically higher than fetal DNA levels in women without labor at
term (p=0 .014) . The same results were found in the groups of preterm
deliveries (28-31wks: p=0 .048 and 32-35wks: p= 0 .003) . A statistically
significant difference was not found in the lower age group (>27wks)
which was probably due to the low number of samples . Furthermore,
a statistically significant increase of fetal DNA during deliveries at term
was found when compared to preterm deliveries (p=0 .05) .
Cff-DNA is increased during spontaneous deliveries at term and preterm
when compared to pregnant women without labor . Therefore, cff-
DNA levels might be used as a marker for preterm deliveries .
P03.34
Prenatal diagnosis of chromosomal abnormalities in tomsk
population
L. P. Nazarenko, S. L. Vovk, Y. S. Yakovleva, N. B. Torchova, M. O. Filippova,
M. P. Korf, N. L. Puryskina;
State Research Institute of Medical Genetics, Tomsk, Russian Federation.
The aim of current study was to evaluate the frequency and structure of
prenatally detected chromosomal abnormalities in Tomsk population .
The risk for chromosomal aberrations was calculated by taking into
account maternal age and gestation time, fist and/or second trimester
serum markers, fist and/or second trimester ultrasound. Cut-off for invasive
testing was risk 1 in 250 . A total of 1349 chordocenteses, amniocenteses,
placentocentesis and chorion biopsies were performed
during the period of 5 years. Karyotype clarification was performed by
conventional cytogenetic analysis . Abnormal karyotypes were found
in 4 .8% of cases . Numerical and structural chromosomal aberrations
were detected in 73 .8% and 26 .2% of cases, respectively .
P03.35
chromosome abnormalities in amniocenteses with normal fetal
ultrasonography
Z. Yilmaz 1 , E. Tarim 2 , O. Ozer 1 , T. Bulakbasi 1 , F. Yanik 2 , F. I. Sahin 1 ;
1 Baskent University Faculty of Medicine Department of Medical Genetics, Ankara,
Turkey, 2 Baskent University Faculty of Medicine Department of Obstetrics
and Gynecology, Ankara, Turkey.
Before 1994, maternal serum screening (MSS) was not offered to
women 35 years of age or older, unless they did not choose to undergo
invasive diagnostic testing for chromosomal abnormalities . MSS
tests are usually performed for detecting trisomy 21 in women under
35 years of age . Their use in women 35 years of age or older has
a detection rate of 67% for all chromosomal abnormalities and 87%
for trisomy 21 . In our study, we evaluated karyotype results of amniocenteses
of women with advanced maternal age (AMA), increased
risk for trisomy 21 on MSS (MSS-DS, first and/or second trimester
tests) and with AMA+MSS-DS . None of the patient groups had fetal
abnormalities detected during ultrasound examination . Among 2231
patients consulted between January 2002 and December 2007, 52
(2 .33%) had chromosome abnormalities . 20 of 817 cases (2 .44%) with
AMA, 23 of 1121 cases with MSS-DS risk (2%) and 9 of 293 cases
with both AMA and MSS-DS risk among (3 .07%) had chromosome
abnormalities . We detected trisomy 21 in 23 cases (7 AMA, 8 MSS-DS
and 8 AMA+MSS-DS), mosaic trisomy 21 in one case with MSS-DS,
mosaic trisomy 20 in one case with AMA, sex chromosome aneuploidies
in 9 cases (6 AMA, 3 MSS-DS), unbalanced rearrangements in 3
cases (1 AMA, 2 MSS-DS), marker chromosome in 3 cases ( 1 AMA,
2 MSS-DS), balanced rearrangement in 12 cases (4 AMA, 7 MSS-DS,
1 AMA+MSS-DS). Although the fetuses had normal findings in fetal ultrasound
examination, pregnancies with increased risks still had chromosome
abnormalities .
P03.36
Hypertelorism-microtia-clefting syndrome, two further prenatal
cases
J. Ghoumid 1 , H. Ansart-Franquet 1 , D. Subtil 1 , N. Pasz 1 , L. Devisme 2 , S. Manouvrier-Hanu
1 , J. Andrieux 1 , M. Holder-Espinasse 1 ;
1 Jeanne de Flandre, Lille, France, 2 Centre de Biologie Pathologie, Lille, France.
Hypertelorism-Microtia-Clefting syndrome (HMC syndrome) is a very
rare autosomal recessive condition, with only nine cases reported in
the literature . It comprises hypertelorism, microtia, cleft lip and/or palate,
microcephaly, variable mental retardation, renal anomalies and
sometimes heart abnormalities .