2009 Vienna - European Society of Human Genetics

Prenatal and perinatal genetics
All the pregnant females were subjected to history taking, pedigree
construction, clinical examination and ultrasound scan. Proper counseling
was done and patients were scheduled for prenatal diagnosis.
4 cases did not come in scheduled time, 3 of them were type II and
one was type IIIb.
5 females (3 type I and 2 type IIIb) came in two successive pregnancies
for prenatal diagnosis to prenatal diagnosis was done in 2 pregnancies
of them as anembryonic sacs were diagnosed. Another female (MPS
VI) came in three successive pregnancies. However prenatal diagnosis
was not performed in two of them as the first was vesicular mole
and the second was anembryonic sac, both ended by evacuation
P05.27
molecular Genetic tests and Referral Reasons in Prenatal
Diagnosis at a tertiary Referral Hospital
E. E. Bilal, A. Alpman, A. Aykut, H. Onay, O. Cogulu, F. Ozkinay;
Ege University Faculty of Medicine, izmir, Turkey.
Prenatal diagnosis is helpful for planning the problems that may occur
in the newborn period and deciding whether to continue the pregnancy.
Single gene mutations as the cause of single gene disorders can
be detected by molecular analysis in the prenatal period. The prevalence
of all single gene disorders at birth is about 10 per thousand. It
is possible to apply the molecular genetic analyses in these patients
for prenatal diagnosis and genetic counseling. Here, we present the
most common requested single gene disorders and molecular genetic
tests in our center.The molecular test results of all prenatal referrals
between 2006-2009 at a tertiary medical center in western part of Turkey
were evaluated retrospectively. Total 121 prenatal samples were
included in the study. Ninety-four of 121 prenatal tests were performed
for beta-thalassemia (77.7%) which was followed by cystic fibrosis in
16 (13.2%), 10 in spinal muscular atrophy (8.3%), 1 in Osteogenesis
imperfecta (0.8%). Because beta-thalassemia is the most common
single gene disorder and one of the most important health problems in
Turkey, particularly, prenatal diagnosis of this disease has become a
widely available test.
P05.28
Prenatal diagnostics in Bulgaria - current experience and future
trends
R. V. Vazharova 1 , S. Baklova 1 , A. Savov 1 , R. Rainova 1 , I. Sinigerska 1 , A. Jordanova
1 , A. Todorova 1 , Y. Petrova 1 , M. Ivanova 1 , A. Bichev 1 , V. Dimitrova 2 , J.
Karagyosova 2 , D. Markov 2 , V. Kincheva 1 , A. Andreev 1 , T. Chernev 2 , S. Ivanov 2 ,
L. Kalaydjieva 3 , I. Kremensky 1 ;
1 National genetic Laboratory, Sofia, Bulgaria, 2 University Hospital of Obstetrics
and Gynecology, Sofia, Bulgaria, 3 Centre for Human Genetics, Edith Cowan
University, Perth, Australia.
Invasive prenatal diagnostics was introduced into medical practice in
the early 70-ies. Since then it is recognized as a useful tool for prevention
of severe human diseases. Prenatal invasive diagnostics for
monogenic and chromosomal diseases in Bulgaria started in 1980.
Since 1996 maternal serum screening for Down syndrome and NTDs
is routinely offered. Now National genetic laboratory has well developed
services providing laboratory prenatal diagnostics of monogenic
and chromosomal diseases in high risk families.
For a 28 years period 400 families with severe monogenic diseases
as CF, DMD/BMD, SMA, beta-Thalassemia, PKU, CMT1A and other
rare metabolic diseases underwent DNA prenatal diagnostics. In 55
families with lysosomal storage diseases prenatal diagnostics was
performed by enzymatic assays. Among all families studied 91 fetuses
were found to be affected. In some families new disease causing mutations
were found.
During the last 5 years rapid growth of prenatal diagnoses for chromosomal
diseases is evident and more than 1000 invasive procedures for
this indication are performed yearly. As an alternative to cytogenetic
analysis Q-PCR for common aneuploidies (trisomy 21, 18 and 13) was
introduced in 1999 and since 2002 is used routinely in our practice.
For 2008 among 490 amniocenteses performed because of risk over
1:250 after maternal serum screening 15 fetuses (3,1%) with trisomy
21 were found.
Since the capacity for cytogenetic analysis is limited and targeted Q-
PCR detects only common aneuploidies the introduction of new technologies
as arrayCGH seems to be a reliable tool for effective prenatal
diagnosis of chromosomal diseases.
P05.29
Evaluation of the fetus with cheilognathopalatoschisis
C. C. Albu, D. F. Albu, M. Dumitrescu, E. Severin;
“Carol Davila” Univ Med Pharm, Bucharest, Romania.
Background: Cheilognathopalatoschisis or complex cleft (involves cleft
of the lip, upper jaw, and hard and soft palates) is a severe birth defect.
It occurs isolated or associated with other medical conditions.
Aim: to determine whether the cheilognathopalatoschisis is syndromic
or non-syndromic.
Patients and Methods: A 29-year-old Caucasian female, pregnant for
the first time, was referred at 17 weeks’ gestation for a routine prenatal
ultrasound. The couple had normal general health and was not
consanguineous. There was no family history of cheilognathopalatoschisis.
Routine ultrasonography at 17 weeks of pregnancy, triple test
(AFP,uE3, hCG), selective ultrasonography for detection of fetal abnormalities,
and amniocentesis were performed.
Results: Ultrasound examination revealed a single fetus with an orofacial
cleft and no other developmental abnormalities. Triple test was not
sensitive to the presence of trisomy 13 but chromosome analysis was
recommended because orofacial cleft as a sonographic marker suggested
the possibility of a chromosomal anomaly. FISH and QF-PCR
detected no aneuploidy in chromosomes X, Y, 13, 18 and 21.
Conclusions: Cheilognathopalatoschisis was diagnosed by performing
3D US in the second trimester of pregnancy. Our results suggested a
non-syndromic cleft. Prenatal evaluation was useful in management,
prognosis and prevented the negative emotional effects of the parents.
P05.30
Angiotensin converting enzyme (AcE) polymorphism and its
role in the neonatal respiratory disease development
K. V. Danilko1,2 , L. I. Khamidullina1 , R. Bogdanova2 , A. I. Fatyhova2 , T. V. Victorova1,2
;
1 2 Institute of Biochemistry and Genetics, Ufa, Russian Federation, Bashkir
State Medical University, Ufa, Russian Federation.
Angiotensin converting enzyme plays an essential role in two physiological
systems, one leading to the production of angiotensin II and
the other to the degradation of bradykinin. The wide distribution and
multifunctional properties of these peptides suggest that ACE could be
involved in various pathophysiological conditions, including neonatal
respiratory distress-syndrome (RDS) and pneumonia. The ACE levels
are under genetic control, and the insertion/deletion (I/D) polymorphism
in intron 16 of the ACE gene is used as a marker for a functional
polymorphism.
We investigated the role of ACE I/D polymorphism on the incidence
of RDS and pneumonia. We studied 161 patients with RDS (n=97),
congenital pneumonia (CP) (n=64) and 286 healthy term neonates
matched by sex from Ufa, Russian Federation, using two primers PCR
for each DNA sample twice.
For all samples, genotype distribution was in Hardy-Weinberg equilibrium.
II genotype frequency was decreased in all patients (19,88%,
p=0.005), including RDS (20,62%, p=0,031) and CP (18,75%,
p=0.038), compared with the healthy term neonates (32,87%). The
RDS patients with D allele (53,09%, p=0,026, OR=1,2), but not the
CP group (51,56%, p=0,12), had the slightly increased risk of disease
(43,53% in healthy term neonates group).
These data suggest a potential role for angiotensin-converting enzyme
polymorphism in the development of neonatal respiratory disease. The
D allele may adversely influence the risk of the RDS development.
However this allele can be associated with birth prematurity of the
RDS patients. So, further study is needed to confirm the association.
P05.31
Respiratory distress syndrome in neonate and association of
polymorphisms surfactant protein D gene
L. Khamidullina1 , R. Fayzullina2 , T. Victorova1,2 , K. Danilko1 ;
1 2 Institute of Biochemistry and Genetics, Ufa, Russian Federation, Bashkir
State Medical University, Ufa, Russian Federation.
The surfactant proteins play important roles in lung function, and genetic
variants of these proteins have been linked with lung diseases,
including respiratory distress syndrome (RDS). The aim of the study
was the investigation of association between polymorphisms of surfactant
protein D gene (SFTPD (Met11Thr, Ala160Thr) and the risk of