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

Prenatal diagnosis
Netherlands.
The detection of a skeletal dysplasia during pregnancy creates an intricate
situation depending on the type of the skeletal dysplasia and the
stage of the pregnancy. Establishing a diagnosis as exact as possible
is important for support and management of the existing pregnancy
and may have consequences for future pregnancies. Due to the time
factor, a diagnosis is not always found during the on-going pregnancy.
Additional information, such as follow-up after birth, skeletal X-rays,
obduction and chromosomal and DNA-investigations is essential in
such a situation. We present one postnatal and two prenatal cases
of a rare skeletal dysplasia, where DNA-investigation confirmed the
subtype of the skeletal dysplasia and generated important information
about prognosis. In one prenatal case, MRI-examination of the
pregnancy gave valuable additional information for the differential diagnosis.
P0485. β-Thalassemia Carrier Screening and Prenatal Diagnosis
among Iranian Population
M. Sajedifar 1,2 , V. Lotfi 1,2 , P. Fouladi 1,2 , A. Joudaki 1 , F. Hashemi 1 , S. Zeinali 1,3 ;
1 Medical Genetics Lab of Dr Zeinali, Tehran, Islamic Republic of Iran, 2 Young
Researchers Club of research and science branch of Islamic Azad University,
Tehran, Islamic Republic of Iran, 3 Human Genetics Unit, Dept of Biotech ,Pasteur
Institute, Tehran, Islamic Republic of Iran.
Thalassemia is one of the most common monogenic disease worldwide
and also in Iran. More than 200 different mutations have been
reported to date, and each ethnic population has it ‘ s own cluster of
common mutations. This is well illustrated by the experience of the
National Thalassemia Screening Program in Iran. Molecular analysis
of β-globin mutations has been performed by PCR-based protocols
(ARMS, RFLP, DNA Sequencing) mostly for prenatal diagnostic in our
center.DNA samples are usually tested for mutations like IVS-II-I, IVS-
I-5, IVS-I-110,codon 5, codon 17,codon 41/42(-TTCT) and many common
mutations and deletions.
In a population of 1954 prenatal diagnosis (PNDs) performed since
mid 2000 and we have found 24% normal, 50.7% β-Thalassemia carriers
and 22.9% affected (β-Thalassemia major).
Prenatal diagnosis has been an ongoing program in Iran since 1996
by a religious decree. Our center is part of the PND Network in Iran
and the above PNDs have been performed as a part of the program to
curtail β-thalassemia.
Keyword: Thalassemia , Prenatal Diagnosis , ARMS , DNA Sequencing
P0486. Quality control of prenatal sonography in detecting
trisomy 18. The value of perinatal autopsy
Z. Szigeti, Z. Csapo, J. Joo, B. Pete, Z. Papp, C. Papp;
First Dept. of Ob/Gyn, Semmelweis University, Budapest, Hungary.
Introduction: Trisomy 18 (Edwards-syndrome) is the second most
common autosomal trisomy. The second-trimester ultrsonographic
examination followed by fetal karyotyping is the most relevant way of
diagnosing this aneuploidy. However, sonographic findings have been
demonstrated to have significant rates of fals-positive and fals-negative
diagnosis. Detailed pathologic examination of aborted fetuses has
important role in the quality control of ultrasonographic diagnosis. This
study was designed to compare the prenatal ultrasound findings and
postmortem pathologic findings of fetuses with trisomy 18.
Materials and Methods: 70 fetuses with trisomy 18 were diagnosed
between 1990 and 2004. Sonographic and autopsy findings were compared
by organ system and their correlation was assigned to 1 of 3
categories.
Results: There were 164 separate major structural abnormalities found
on autopsy. Of them, sonography detected 72 (43.9%). Among major
defects the agreement was more than 75% of all abnormalities
of these systems: central nervous system (80%), abdominal abnormalities
(87.5%) and cystic hygroma (100%). Whereas, the sensitivity
of sonography was lower in these organ systems: cardiac system
(66.6%), facial abnormalities (26.3%), urinary system (27.3%) and extremities
(8.7%). The rate of additional findings at autopsy was 56.1%
and involved mainly 2 organ systems: face (including ear) and extremities
(including hands and feet). Some ultrasound findings (n=15) were
not confirmed at autopsy in our series.
Conclusions: This study confirms that perinatal autopsy provides additional
information in many fetuses with trisomy 18. In addition, exam-
1 2
ining the correlation between sonography and pathologic findings may
indicate potential markers for sonographic screening of trisomy 18.
P0487. Characteristics of pregnancies with cytogenetic
diagnosis of trisomy 21.
K. Keymolen, E. Sleurs, I. Liebaers, C. Staessen;
University hospital, Brussels, Belgium.
Aim of the study: In this study we characterize the pregnancies with
cytogenetic diagnosis of trisomy 21.
Materials and methods: We retrospectively looked at pregnancies in
which trisomy 21 was found in chorionic villus sampling (CVS) or amniocentesis
(AC) between 01.01.2002 and 31.12.2006. Data on maternal
and paternal age ,reason for referral, fetal sex, fetal and parental
karyotype were recorded.
Results: In this 5 year period, 73 prenatal cytogenetic diagnoses of
trisomy 21 were made in our centre. It concerned 44 chorionic villus
biopsies and 29 amniocenteses. In all but one case, there was free
trisomy. Mosaic trisomy was present in 3 cases. Forty-one trisomic
fetuses were male and 32 female. The main reason why cytogenetic
diagnosis was performed, was maternal age (31/73), fetal anomalies
on ultrasound (18/73) and second trimester serum screening (7/73). In
13 pregnancies there were 2 different reasons for referral.
The mean maternal age was 36 years, the mean paternal age 37.1
years.
For 53 parents, a karyotype was performed, being normal for 52 and
showing a translocation for 1.
Discussion: Trisomy 21 is the most common chromosomal anomaly
encountered in CVS or AC. Despite the small sample of this study, the
experience in our centre confirms the common knowledge that it occurs
more frequently in older parents and that in more than half of the
cases there is an anomaly on ultrasound and/or biochemistry. For the
majority of the pregnancies for which follow-up was available, termination
of pregnancy was performed
P0488. Prenatal diagnosis of a marker chromosome derived
from chromosome 3 in a fetus with growth retardation and
microcephaly- a case report
M. I. Srebniak, P. dos Santos, P. Noomen, D. Halley, R. van de Graaf, L. Govaerts,
R. Galjaard, D. Van Opstal;
Erasmus Medical Center, Rotterdam, The Netherlands.
We present a rare prenatal case of an “incomplete” trisomy 3 rescue
which resulted in an extra chromosome 3-derived marker chromosome
in the foetus.
The patient was referred for prenatal cytogenetic diagnosis in chorionic
villi because of advanced maternal age and a growth discrepancy
between both foetuses in her twin pregnancy, with foetus II being too
small for the gestational age.
Whereas foetus I had a normal male karyotype, STC-villi of foetus II
showed 100% trisomy 3 and in LTC-villi an extra marker chromosome,
derived from chromosome 3, was found in all analysed cells. In order
to exclude confined placental mosaicism follow-up investigations in
amniotic fluid cells were performed which showed the marker chromosome
to be present in 100% of the cells. Parental karyotypes were
normal.
FISH- and DNA-studies that were performed in order to characterize
the marker chromosome and to elucidate the mechanism of formation,
respectively, as well as the clinical data of the foetus will be presented.
P0489. The incidence of prenatally diagnosed Turner syndrome
and their referral indications
M. Akgul 1 , E. Ataman 1 , B. Durmaz 2 , A. Alpman 2 , E. Karaca 2 , O. Cogulu 2 , H.
Akin 1 , C. Gunduz 3 , C. Ozkinay 1 , F. Ozkinay 2 ;
1 Ege University, Faculty of Medicine, Department of Medical Genetics, Izmir,
Turkey, 2 Ege University, Faculty of Medicine, Department of Pediatrics, Izmir,
Turkey, 3 Ege University, 3Ege University, Faculty of Medicine, Department of
Medical Biology, Izmir, Turkey.
Turner syndrome occurring in 1/2000-5000 female live births is one of
the most common chromosomal disorder. It is also a common reason
in spontaneous miscarriages with an incidence of 10%. As 99% of embryos
with 45,X karyotype result in spontaneous abortion, only 1% of
Turner syndrome fetuses survive till birth. Increased nuchal translucency,
cystic hygroma, and renal and cardiac defects are typical findings