European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Prenatal diagnosis
sions regarding the pregnancy. For the physician, prenatal diagnosis
provides vital information that can be utilized for better patient’s management.
Prenatal knowledge about genetic abnormalities enables
the physician to tailor or manage the timing and mode of delivery for
optimal maternal and fetal outcomes.
Great efforts have been put forth to devise more efficient genetic protocols.
Because of its ability to provide results early in pregnancy, firsttrimester
screening is becoming increasingly more important. First-trimester
screening provides the opportunity for early risk assessment
and early diagnosis of fetal aneuploidy via chorionic villus sampling
(CVS). Early diagnosis allows for pregnancy termination earlier in gestation,
if the patient so desires,
While the advances in first-trimester genetic test are exciting, there will
always be a role for second-trimester genetic test. Many patients may
not present in time for first-trimester test. Likewise, many patients may
not have access to providers skilled at CVS. In addition, a portion of
patients may prefer amniocentesis to CVS.
In this talk, available genetic techniques for prenatal diagnosis in Iran
will be discussed. In addition, from the prenatal diagnosis experiences
in Iran, several other concerns noticed by genetecian such as fairness
of access to genetic services, indications for prenatal diagnosis, confidentiality
problems etc will be mentioned.
P0476. Needs assessment regarding decision about Down’s
syndrome prenatal testing: A systematic review of women, their
relatives and health professionals’ perceptions.
F. Légaré1 , S. St-Jacques2 , S. Grenier2 , M. Charland1 , J. Forest1 , F. Rousseau1 ;
1CHUQ Research Center, CanGeneTest consortium, Québec, PQ, Canada,
2CHUQ Research Center, Québec, PQ, Canada.
Background: Population-based prenatal testing for Down’s syndrome
is being considered in the Province of Quebec. In order to elaborate
effective decision support interventions, a systematic review was
performed to identify the needs of women, their relatives and health
professionals regarding decisions about prenatal testing for Down’s
syndrome.
Methods: PubMed, EMBASE, CINHAL and PsycINFO were searched
for original studies in English or French. Studies were identified independently
by two reviewers and discrepancies were resolved by a third
one. Studies were included if they reported original data on difficulties
and/or facilitators in making decisions about Down’s syndrome prenatal
testing, enrolled women, their relatives and/or health professionals
and were conducted in real clinical situation. Content analysis is being
currently performed by two reviewers using a taxonomy adapted from
the Ottawa Decision Support Framework and quality of studies, assessed
using Qualsyst validated tools.
Results: From 2390 potential titles, 64 publications covering 51 unique
studies were included. The majority of studies were from UK (27%)
followed by Canada and USA (12% each). Most targeted screening for
Down’s syndrome (41%). Most used qualitative methods exclusively
(45%). Three studies were grounded in theory. Validated measurement
tools were used in ten studies. Overall, the vast majority of studies
targeted women (90%) followed by health professionals (12%) and
partners (10%).
Conclusions: We observed an important gap in knowledge about the
perceptions of health professionals and relatives. In order to elaborate
effective decision support interventions for prenatal testing for Down’s
syndrome, future studies will need to address these gaps.
P0477. A supernumerary marker chromosome with a related
pseudodicentric chromosome detected in a fetus during
prenatal diagnosis
S. Karymee 1 , F. Mahjoubi 2 , M. Khalegian 1 , S. Tootian 1 , M. Akbari 3 ;
1 1Medical Genetic Laboratory of Akbari, Taleganee St, Tehran, Iran, tehran,
Islamic Republic of Iran, 2 1Medical Genetic Laboratory of Akbari, Taleganee St ,
Tehran, Iran &NIGEB, tehran, Islamic Republic of Iran, 3 1Medical Genetic Laboratory
of Akbari, Taleganee St, Tehran, Iran& 3Clinical genetic Dept. Tarbiat
Modaress University, Tehran, Iran, tehran, Islamic Republic of Iran.
Dicentric autosomes are considered as unstable constitutional chromosomes
in humans. The presence of centromeres on the same chromosome
leads to a high risk of attachment of the same chromatid to
the mitotic spindle from opposite poles and to the formation of anaphase
bridge during cell division. Therefore, breakage of the dicentric
can occur.
1 0
We describe a fetus in which a minute supernumerary marker chromosome
(SMC) was detected in addition to a larger pseudodicentric chromosome.
The case was a 12-week fetus with mosaicism for a normal
and two abnormal cell lines: one had a dic (12;15)(q11.2;q11.2) chromosome,
and the other had a minute SMC. Although the heart beat
could be detected at the beginning of the pregnancy, the heart failed to
fully develop and therefore therapeutic abortion was done at 16 weeks
of gestation. Deletion of centromeric material was proposed as one
mechanism of centromere inactivation in dicentric chromosomes. This
SMC may be the result of a deletion event leading to inactivation of one
centromere of a dicentric chromosome to generate a pseudodicentric
chromosome. Therefore, this case suggests possible mechanisms for
the origin of this SMC
P0478. Prenatal diagnosis of aneuploidies of chromosomes 13,
18, 21, X and Y by QF-PCR in the Republic of Macedonia
D. Plaseska-Karanfilska, S. Talaganova, S. Trivodalieva, G. D. Efremov;
Macedonian Academy of Sciences and Arts, Research Center for Genetic
Engineering and Biotechnology, Skopje, The former Yugoslav Republic of
Macedonia.
The great majority of chromosomal abnormalities are due to aneuploidies
of chromosomes 21, 18, 13, X and Y. The quantitative fluorescent
(QF) PCR of selected small tandem repeat (STR) markers enables
rapid and accurate prenatal diagnosis of these aneuploidies. Here, we
present our results of the use of QF-PCR for prenatal detection of common
chromosomal aneuploidies in 930 pregnancies at risk. The prenatal
diagnosis was performed on genomic DNA isolated from fetal cells
collected by amniocentesis and chorionic villus samples. All samples
were analyzed by three multiplex PCR assays, amplifying a total of
thirteen STR markers on chromosomes 21 (D21S1435, D21S1446,
D21S1411 and D21S1414), 18 (D18S535, D18S1367, D18S978 and
D18S386), 13 (D13S631, D13S258 and D13S1817) and X (DXS6803
and XHPRT). When these markers were uninformative, additional
markers were used. Using this approach, we have detected 17 fetuses
with trisomy 21, 11 with trisomy 18, one with partial trisomy 18, four
with trisomy 13, three fetuses with Turner syndrome (45,XO) and one
with Klinefelter syndrome (47,XXY). A polymorphic duplication was detected
in two fetuses with STR marker D13S631; in both fetuses it was
inherited from one of the parents. The parental origin of the aneuploidy
was determined in 11 cases with trisomy 21, seven with trisomy 18,
three with trisomy 13 and three with Turner syndrome. The origin was
maternal in all complete trisomies and paternal in the partial trisomy
18 and the Turner syndrome cases. Triple X syndrome (47,XXX) was
detected in a woman with a fetus with trisomy 18.
P0479. QF-PCR on Amniotic Fluid and Corionic Villi. Diagnostic
troublesome results.
C. Curcio 1 , V. Tieran 1 , F. Lalatta 2 , S. Guerneri 1 , P. De Leonardis 1 , M. Travi 1 , A.
Kustermann 3 , D. A. Coviello 1 ;
1 Laboratorio di Genetica Medica, Fondazione IRCCS, Ospedale Maggiore
Policlinico, Mangiagalli e Regina Elena, Milan, Italy, 2 Servizio di Genetica Medica,
Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Regina
Elena, Milan, Italy, 3 Cenro di Diagnosi Prenatale, Seconda Clinica Ostetrico
Ginecologica, Università di Milano, IRCCS Fondazione Ospedale Maggiore
Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
Autosomal trisomies, which account for about 80% of significant abnormalities,
can be detected within 24-48 hours by quantitative fluorescence
(QF)-PCR. In the last four years we have used QF-PCR
to assess relative allele dosage at polymorphic loci of chromosomes
13, 18, 21 and sex chromosome in more then 3.000 samples (80%
amniotic fluid and 20% Chorionic Villus Samples-CVS). Samples of
women with abnormal ultrasound referrals or from families with known
chromosome rearrangements require full karyotype analysis, but if abnormalities
are identified earlier this will aid the clinical management
of pregnancy and will help to minimize the period of parental anxiety
while awaiting for the diagnostic test result.
Mosaicism in CVS is well documented in the literature and it is detected
in 1-2% of the CVS. Discrepancy between chromosome analysis
of direct short-term cultures (cytotrophoblast cells) versus long-term
cultures (mesenchymal cells) is very well known.
We describe here cases in which a discrepancy between QF-PCR
and standard karyotype was observed in CVS analysis. In two cases
QF-PCR showed the polymorphic markers of two X chromosomes (in