2009 Vienna - European Society of Human Genetics

Prenatal and perinatal genetics
This was the largest study of population SMA carrier screening. Antenatal
population carrier screening for SMA is feasible, effective and
reasonable.
P05.36
Urge of prenatal diagnosis in modernized civilization
B. B. Ganguly, D. Chakrabarti;
MGM Centre for Genetic Research & Diagnosis, Navi Mumbai, India.
Industrial revolution and modernization of medical sciences has contributed
largely to expand the population and extend human lifespan.
Massive quantities of toxic wastes are dispensed in the atmosphere
unchecked as a direct consequence of our dependence on fossil fuels
and advanced technologies which are rendering adverse effects on
the nature. The recent decade has seen an unprecedented rise in natural
calamities due to drastic fluctuations in weather conditions. These
factors yield cumulative stress on the population causing tremendous
damage to their health and well being. Infertility among adults, disorders
like diabetes, cancer, HIV - AIDS, faulty births of infants having
congenital abnormality and/or mental disorders are increasing at an
alarming rate reducing the productive efficiency and profit derivative
of the society.
Hence it is the need of the hour to provide a strong and healthy start to
the future generations so that they can cope up with the ever increasing
hardships. This can be assured if the new born children are free
of debilitating ailments acquired before or during parturition. Prenatal
diagnosis is already a routine measure to screen and prevent birth of
genetically impaired children in well informed societies. However, this
practice is limited at large due to lack of awareness among developing
nations and availability of skilled diagnostic services in cost-effective
manner. Conventional cytogenetics is one field of study that can prove
to be an effective mode of prenatal diagnosis which should be given
impetus by the organizations monitoring global health to bring immediate
redress.
P05.37
Exposure to Fluoroquinolones during Pregnancy: An Analysis of
Birth Outcomes from a Romanian Pregnancy cohort study
V. Dumitrascu 1 , A. Matusz 2 , C. Iftode 2 , A. Cheveresan 1 , D. Vlad 3 , C. Gug 4 ;
1 “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania,
Timisoara, Romania, 2 Scientific Secretariat, Association of General Health Care
Providers, Timis County, Romania, Timisoara, Romania, 3 Emergency Clinical
County Hospital, Timisoara, Romania, Timisoara, Romania, 4 Department of
Medical Genetics, “Victor Babes” University of Medicine and Pharmacy, Timisoara,
Romania, Timisoara, Romania.
Background: The new fluoroquinolones have favorable pharmacokinetic
properties and high affinity for immature cartilage and bone tissue.
Objective: to evaluate the teratogenic risk following gestational exposure
to fluoroquinolones, numbers of fetal deaths, distress, and the
development of the toddler’s skeleton at the age of twelve month.
Methods: A longitudinal, randomized, 6 year comparative study, from
November 2002 to December 2008, was conducted in two primary
medical care centers. We followed up 110 women exposed to anti-infective
drugs during gestation, divided in 2 groups: a study group of 58
(52.72%) who took ciprofloxacin, norfloxacin, or ofloxacin for different
infections and a control group of 42 (38.18%) exposed to macrolides.
Results: 23 women (25.21%) took fluoroquinolones in the first trimester
of pregnancy, and there was a higher rate of therapeutic abortions
among the study group (8 of 58 versus 3 of 42 - for the control group).
Rates of major congenital malformations didn’t differ between the two
groups (relative risk, 0.88; 95% confidence interval, 0.27 to 3.29). The
major malformations from the quinolone group were: hip displasia, hypospadias
and ventricular septal defects, occurred after fluoroquinolone
exposure during organogenesis. The relationship between fluoroquinolone
exposure and arthropaty focused on the newborn’s cartilage
status (craniotabes) and on long-term musculoskeletal dysfunctions
until at the age of twelve month (diastasis recti and genu valgum).
Conclusions: Gestational fluoroquinolone exposure is risky in the first
trimester of pregnancy. Ultrasonography is needed to monitor the fetal
development, followed by long-term musculoskeletal survey.
P05.38
Recurrent trisomy 21: Postzygotic formation of i(21q) from both
maternal chromosomes 21
M. Trková, N. Jenčíková, M. Putzová, D. Rašková, D. Stejskal;
The Centre of Medical Genetics and Reproduction Medicine GENNET, Prague,
Czech Republic.
Structural rearrangements involving chromosome 21 are responsible
for 5% of trisomy 21 cases. The majority of rea(21q;21q) are, in fact,
isochromosomes - i(21q) and only a small percentage are true Robertsonian
translocations. The recurrence of de novo structural and
numerical/structural chromosomal rearrangements might have three
major reasons: a) recurrence by chance; b) gonadal mosaicism and c)
low-level somatic-gonadal mosaicism in one parent.
We present a family with recurrent trisomy 21 in three consecutive
pregnancies with maternally derived rea(21q;21q) in all cases. Extensive
G-banded karyotyping and FISH analysis of the maternal peripheral
blood revealed trisomy 21 mosaicism (1.5% cells were trisomic for
chromosome 21). Gonadal mosaicism for trisomy 21 in a significant
proportion of mother’s ovarian cells provides a plausible explanation
for her obstetric history.
Molecular studies using highly polymorphic short tandem repeat (STR)
markers localised on chromosome 21 permitted constructions of haplotypes
in three patient foetuses from three consecutive pregnancies.
It revealed trisomy 21 was due to the isochromosomes, thus strongly
suggesting their postzygotic origin. Most surprisingly, molecular analysis
also demonstrated that isochromosomes in two cases originated
from different maternal chromosomes 21.
Moreover, pregnancy outcome was also influenced by partners’ consanguinity.
After two unsuccessful attempts of IVF-PGS they got spontaneously
pregnant. The child with normal chromosome 21 suffered
from an autosomal recessive disorder (LCHAD / long chain 3-hydroxyacyl-CoA
dehydrogenase deficiency) as a direct consequence of consanguinity.
To our knowledge, we demonstrate the first case of mosaics with two
different maternal i(21q) derived from both maternal chromosomes
21.
P05.39
the analysis of mitochondrial DNA polymorphism in
monozygotic twins
K. Wielgus 1 , K. Cieslik 2 , M. Waszak 2 , M. Szalata 3,4 , R. Slomski 3,4 ;
1 Institute of Natural Fibres and Medicinal Plants, Poznan, Poland, 2 University
School of Physical Education, Poznan, Poland, 3 Poznan University of Life Sciences,
Poznan, Poland, 4 Institute of Human Genetics, Polish Academy of Sciences,
Poznan, Poland.
Since the elucidation of the mitochondrial genome sequence in 1981,
nearly 200 pathogenic point mutations, deletions, insertions and rearrangements
have been described and associated with a variety of
mtDNA-related human diseases. Due to unique twin genetics, twins
have been identified as an ideal subject for observations of complex
diseases inheritance. Still, so far no wide range analysis of mtDNA in
twins has been reported. In this study the analysis of mitochondrial
DNA polymorphism in group of monozygotic twins was performed,
using umblical cord blood. Zygosity of twins was determined by the
analyses of DNA fingerprinting and mini- and microsatellite polymorphism
(hybridization, PCR). The SSCP and HD analyses of D-loop
mtDNA reveal a high polymorphism of this region. However, within the
analyzed group of twins, no differences were found in either pair of
monozygotic twins. T>C transition was detected in mtDNA sequence
in one pair of twins. The resultant tract of 10 C preceded by 4 A seems
to be related to heteroplasmy of mitochondrial genome.
P05.40
Outcome of fetuses with a sonographic finding of echogenic
bowel.
V. Scotet1 , I. Duguépéroux1,2 , M. P. Audrézet1,2 , M. Blayau3 , C. Férec1,2 ;
1 2 Inserm U613, Brest, France, Dept. of molecular genetics, Hospital, Brest,
France, 3Dept. of molecular genetics, Hospital, Rennes, France.
Introduction: Routine medical follow-up of pregnancies and development
of ultrasonography have enabled the sonographic finding of fetal
echogenic bowel (FEB), a sign that has been associated with various
pathologies. Based on the experience of Brittany (western France),
this study reports the type and frequency of the pathologies diagnosed
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