2009 Vienna - European Society of Human Genetics

Prenatal and perinatal genetics
from the fourth pregnancy combined with amniotic fluid investigation
of the fifth pregnancy using glycosaminoglycan electrophoresis and
lysosomal enzyme activity measurements confirmed beta-glucuronidase
deficiency in both. Cord blood investigation revealed prominently
vacuolated monocytes, with basophilic inclusions in lymphocytes
(Gasser cells) and metachromatic granules (Alder-Reilly bodies) in
granulocytes. Electron microscopic investigations showed vacuolated
Hofbauer cells in the placenta and foamy macrophages in spleen, liver,
and other organs. Greatly reduced activity of beta-glucuronidase in
cultured skin fibroblasts reconfirmed the diagnosis of MPS type VII and
GUSB DNA analysis is still pending. We can conclude that recurrent
massive non-immune hydrops foetalis is likely autosomal recessive
with 25% recurrence risk in which lysosomal storage disorders need
to be investigated.
P05.22
Achivements in the NiPD of monogenic disorders: a prenatal
diagnosis unit experience
A. Bustamante Aragones 1,2 , C. Gonzalez Gonzalez 3 , M. Rodriguez de Alba 1,2 ,
E. Vallespin 4 , M. Garcia Hoyos 1,2 , J. Gallego Merlo 1,2 , E. Ainse 1,2 , C. Perez
Cerdá 5,2 , M. Trujillo Tiebas 1,2 , C. Ramos 1,2 ;
1 Fundacion Jimenez Diaz-Capio, Madrid, Spain, 2 CIBERER, Spain, 3 Megalab,
Madrid, Spain, 4 Hospital La Paz, Madrid, Spain, 5 Universidad Autónoma de
Madrid, Madrid, Spain.
Non-invasive prenatal diagnosis (NIPD) using fetal DNA in maternal
plasma has proven its potential for the study of the fetus. Many diagnostic
units are currently offering non-invasive fetal sex assesment for
X-linked disorders and Rh determination in Rh(-) pregnant women.
As for the monogenic disorders, since the fetal DNA circulates within a
high background of maternal DNA, NIPD is mainly based on the study
of paternal alleles, absent in the maternal genome. This limits this approach
to pregnancies in which the father is carrier of an autosomal
dominant mutation or those in which both parents are carriers for different
autosomal recessive mutations.
The clinical incorporation of NIPD for monogenic disorders must fulfil
the same needs of the conventional molecular prenatal diagnosis.
We have studied 14 paternal mutations associated to different diseases:
X-linked retinitis pigmentosa, congenital Leber amaurosis, cystic
fibrosis, propionic acidemia and Huntington disease.
The diagnosis was performed by the use of different analytical methods
currently used in the clinical practice.
The fetal condition for the paternal mutation was correctly diagnosed
in 13 out of the 14 cases. The remaining case could not be diagnosed
due to the length of the mutant allele.
NIPD of monogenic diseases could be the forthcoming study to be offered
in clinical practice. The study of monogenic disorders in maternal
plasma must be individualized and directed. As a Prenatal Diagnosis
Unit we are aware of the importance of having different diagnostic tools
available to get to a reliable diagnosis for each individual case.
P05.23
A case of partial trisomy 3q in a fetus
O. Nikolayeva, L. Bogodukh, T. Petrova, S. Ripp;
Family Planning and Reproduction Centre, Astrakhan, Russian Federation.
A married couple underwent cytogenetic testing following the detection
of abnormalities in a fetus 25 weeks. The father was 22 years old,
the mother was 23 years old, and this was their 3 rd pregnancy. Fetal
ultrasound had revealed multiple congenital abnormalities including
congenital heart disease, common arterial trunk, a 4mm defect of interventricular
septum, and Dandy-Walker syndrome. The mother’s karyotype
was 46,xx, inv (3) (p2.5 q2.1). Cordocentesis allowed karyotyping
of the fetus and revealed: 46,xx,der(3) (3qter-cen 3p2.5::3q2.1-3qter),
resulting in partial trisomy of the long arm of the 3 rd chromosome as
a result of recombination inv(3) by the mother. The pregnancy was
subsequently aborted. Fetal pathology revealed: body mass 570g,
length 21cm. The sex was indeterminate. There was acrocephaly, high
forehead, and hypertelorism. The nose is small and flat with broad
nostrilis, and the bridge was sunken. The ears were low.
The fetus also had contracture of knee and talocrucal joints. The lower
limbs were adducted to the trunk, and there was lower limb syndactyly.
The upper extremities are without pathology. There was agenesis of
the urinary bladder, the ureters flowing into a broadened rectum. No
internal sexual organs were detected.
P05.24
Overview of Prenatal Diagnosis (PND) in our country (iran)
M. H. Kariminejad, Azadeh Moshtagh, Farnaz Azimi, Nasrin
NabaviNia,Mahnaz Pirveissi,Narges Miraftabi,Roxana Kariminejad;
Kariminejad & Najmabadi Pathology & Genetics Center, Tehran, Islamic Republic
of Iran.
Prenatal diagnosis became a generally accepted tool for prevention of
genetics disorders since the 1980s. Simultaneously Iranian geneticists
and clinicians of related fields attempted to establish this procedure in
our country.
It was a great challenge, it took a long time to be overcome the problems,
including legal approval initially granted for hemoglobinopathies
at 1996 and thereafter for other genetic disorders including chromosomal
abnormalities, metabolic diseases MPS, lipid lysosomal storage
diseases: Single aminoacids, muscular dystrophies, myopathies
(SMA), triple nucleotide repeats, Skin lesions and mitochondrial diseases.
Hereby the results, and the practical problems encountered in eleven
thousand chromosomal study of amniotic fluid samples are presented.
The pregnant ladies are classified according to clinical indications as
follows: Maternal age over 30 years, history of offspring with chromosomal
aberration, the similar group with advanced maternal age, balanced
chromosomal aberration in either parents, loss of offspring pre
or postnatal death, high sick of chromosomal abnormalities according
to triple, quadruple, and 1 st trimester fetal screening tests.
P05.25
Prenatal Down’s syndrome screening in st.Petersburg in 2008
T. K. Kascheeva 1 , Y. A. Nikolaeva 1 , M. V. Krechmar 1 , N. V. Vokhmyanina 2 , T. V.
Kuznetzova 1 , O. P. Romanenko 2 , V. S. Baranov 1 ;
1 Ott’s Institute of Obstetrics and Gynecology RAMS, Saint-Petersburg, Russian
Federation, 2 City Medical Genetic Center, Saint-Petersburg, Russian Federation.
There is a growing interest in the shift of prenatal screening to the
first trimester. Such screening relies on the maternal age, free β-hCG,
PAPP-A plus NT. The second trimester screening in Saint-Petersburg
is performed for all pregnant women before 35, the first trimester
screening - for all at the age 35 and more. Since 2004 combined
screening was initiated in Saint-Petersburg. Down syndrome (DS) detection
rate was 94.5% (52/55) (cut off 1/250, FPR 5.8%). Altogether
42111 (82.5%) pregnancies were tested in 15-17 weeks. Detection
rate in 2-d trimester was 75% (24 of 32) (1/360, FPR 7.0%). 2705 of
pregnant women of 35 age and more (36%) were tested in first trimester.
Detection rate in 1-t trimester was 100% (17 of 17) (1/250, FPR
16.0%). Many women from them participated in the both screenings.
Since 2008, February the simple calculation formula has been suggested
for DS risk estimation in the women subjected to both screening
tests. According to this formula the final risk is equal to the risk of
the 1st trimester multiplied by the risk of the second one and divided
by age risk. In that case the number of FPR reduces almost twice. But
application of two steps screening is economically unjustified. Second
screening could be recommended only to the women with risk about
0.05 and 0.4% after the 1 st trimester screening. This group contributed
only 17% of all pregnancies in 2008. More sophisticated decision concerning
application of contingent screening could be taken after some
economical considerations.
P05.26
Prenatal diagnosis of mucopolyssaccharidoses in Egypt:
counseling aspects, sampling techniques and biochemical
diagnosis
E. M. A. F. Fateen1 , A. A. L. A. Aboul Nasr2 ;
1 2 National Research Centre, Cairo, Egypt, Cairo University, Cairo, Egypt.
Objective: prenatal diagnosis of mucopolysaccharidoses in pregnant
females with previously affected child
Subjects: The present study included 35 pregnant females with previously
affected MPS child or more. 10 type I (Hurler), 9 type II (Hunter),
5 type IIIb (Sanfilippo), 3 type IVa (Morquio) and 8 type VI (Maroteaux-
Lamy)
Consanguineous marriage was present in 30 (85.7%) couples. 15
families have no normal children and 20 families have normal children.
However families with no normal males are 27.