2008 Barcelona - European Society of Human Genetics

Cytogenetics
biologic (cytogenetic) indication of radiation injury may specify radiogenic
character of TGC . Results of radiation epidemiological and cytogenetic
examinations at liquidators of the Chernobyl accident consequences
have confirmed the radiogenic character of TGC developed
at the group of radiated persons .
Increase in frequency of malformations among endocrine pathologies
from 1,4 % in 1993 up to 8,9 % in 2001 (more than in 6,3 times) was
registered .
It was revealed the correlation of frequency of chromosomal aberrations
- radiation markers (dicentrics and rings) in peripheral blood
lymphocytes with radiation doze (correlation coefficient - 6,0) in the
remote terms after accident in this group of patients .
Mean value of chromosomal aberrations frequency at group of TGC
patients living in territories with high density of radioactive pollution
exceeds more than 2 times spontaneous level value .
Assignment to TGC patients thymine preparations is recommended in
connection with the radioprotective action registered on level of chromosomal
aberrations in somatic cells, and also with the purpose of
improvement of quality of patient life based on effective hormonal homeostasis
rehabilitation after erasion of thyroid gland .
P02.115
individual chromosomal radiosensitivity of human lymphocytes
as a parameter of cancer risk
N. Ryabchenko, E. Dyomina;
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
of NAS of Ukraine, Kyiv, Ukraine.
Cytogenetic methods based on chromosome aberrations analysis
(G2-assay) make it possible quantitative estimation of radiation effects
on human organism taking into account its individual peculiarities and
thus to estimate its IR . The main basis for application of cytogenetic
methods in radiobiology are high radiosensitivity of human PBL and
formation of stage specific radiation-induced chromosomal aberrations
. From the other hand elevated levels of chromosomal aberrations
are considered to be the proven markers of cancer development in the
calculations of cancer risk after exposure to ionizing radiation . The aim
of the presented work was evaluation of chromosomal radiosensitivity
of healthy individuals and determination those with the increased susceptibility
to radiogenic pathologies .
On the basis of the obtained “stage-effect” and “dose-effect” dependencies
for chromosomal aberrations modifications of G2-assay were
developed. Analysis (in the first mitosis) of chromosomal aberrations
levels induced by G2 irradiation (1,5 Gy) of PBL cultures of 110 healthy
individuals revealed their high interindividual variability . The highest
differences were registered for chromatid breaks which predominated
in the spectrum (CV= 37,5%) . Statistical analysis of the distributions
of the obtained individual cytogenetic parameters indicated bimodality
and make it possible to reveal 12% individuals with increased chromosomal
radiosensitivity . Cytogenetic evaluation of individual chromosomal
radiosensitivity based on G2-assay has its perspectives in the
formation of groups with increased risk of radiogenic cancer developing
and its primary prophylactics among healthy population .
P02.116
clinical cytogenetics study in Pediatric Pathology: A
comparison with Unselected studies
J. M. Pina-Neto, D. Ortolan, L. F. Mazzucatto, V. Bitar, L. C. Peres;
School of Medicine of Ribeirão Preto, Ribeirão Preto, Brazil.
We studied 1558 pediatric autopsies . 33 .1% had congenital anomalies
. Cytogenetic evaluation was successfully performed in 298 . Based
on clinical criteria, karyotyping was performed in cases of isolated malformations
and in cases of two malformations when presenting minor
anomalies and in cases of multiple congenital anomalies except in
those cases due known monogenic disorder .
The distribution by age was: 142(47 .6%) perinatal deaths, 37(12 .4%)
late neonatal, 87(29 .9%) postneonatal , 26(8 .7%) preschool age ,
3(1%) school age , and 1(0 .3%) an adolescent .
We collected blood from superior sagittal sinus, skin and fascia from
the rectus abdominis muscle .
We studied 206 cases of isolated malformations and 34 with two malformations
and none presented any chromosomal anomaly . In the
256 cases of multiple anomalies were detected 70 with chromosomal
anomalies . Among the cases of perinatal death there were 24 chro-
mosomal anomalies, of those 17(70 .8%) were autosomal trisomies,
4 (16 .6%) were structural anomalies, 2 cases (8 .8%) were triploidies
and 1 case was a mosaic 46,XY/47,XY +mar . There were 46 chromosomal
anomalies among the cases of postneonatal death, of those
39(84 .8%) were autosomal trisomies, 5 cases of structural anomalies
and 2 cases of mosaics with chromosomal markers .
The best combination for metaphases obtention was fascia and skin .
The frequency of chromosomal anomalies was 4 .5% (70/1558) very
similar to unselected studies, but if we consider only the perinatal
deaths was 2 .9%(24/835) which is lower when compared with unselected
studies ( 5 .9%) . Will be discussed the results comparing with
unselected studies .
P02.117
chromosomal mosaicism in spontaneous abortions: a casecontrol
study of 500 consecutive chorionic villus samples by
interphase FisH (i-FisH)
S. G. Vorsanova 1,2 , I. Y. Iourov 1,2 , A. D. Kolotii 1 , E. A. Kirillova 3 , V. V. Monakhov
2 , I. A. Demidova 1,2 , A. K. Beresheva 1,2 , V. S. Kravets 1 , O. S. Kurinnaya 1 , I.
V. Soloviev 2 , Y. B. Yurov 1,2 ;
1 Institute of Pediatrics and Children Surgery, Rosmedtechnologii, Moscow, Russian
Federation, 2 National Research Center of Mental Health, RAMS, Moscow,
Russian Federation, 3 Woman’s Medical Center, Moscow, Moscow, Russian
Federation.
Spontaneous abortions (SA) commonly arise from chromosomal
abnormalities, which are usually assessed by standard cytogenetic
techniques. This suggests significant underestimation of chromosomal
mosaicism and application of interphase molecular cytogenetic
techniques (i .e . FISH) for uncovering the true occurrence of mosaics
among SA . We have analyzed 500 consecutive chorionic villus samples
derived from SA by interphase FISH (I-FISH) with DNA probes
for chromosomes 9, 13/21, 14/22, 15, 16, 18, X and Y . Chromosome
abnormalities were found in 50% of cases . We detected aneuploidy
in 39 .6% of samples (aneuploidy of chromosome 16 - 10%; monosomy
of chromosome X - 8 .2%; polysomy of chromosome X - 5 .2%;
aneuploidy of chromosome 13 or 21 - 5%; aneuploidy of chromosome
14 or 22 - 4 .6%; aneuploidy of chromosome 15 - 3 .2%; aneuploidy
of chromosome 18 - 2 .2%; aneuploidy of chromosome 9 - 1 .2%) .
Polyploidy was found in 10 .2% of cases . One case was a chimera
with multiple aneuploidies (case reported in Vorsanova et al ., 2006) .
Multiple chromosome abnormalities manifested as aneuploidy involving
both autosomes and sex chromosomes was detected in 3 .7% of
cases . Chromosomal mosaicism (aneuploidy/polyploidy affecting at
least 5% of cells) was detected in 23 .6% of all cases and 47 .6% of
cases with chromosome abnormalities . To the best our knowledge, the
present set of SA samples is the largest one analyzed by I-FISH . Our
data demonstrate that chromosomal mosaicism is highly frequent and
provide evidence that chromosomal mosaicism is better to study by
I-FISH, rather than alternative approaches . Supported by Philip Morris
USA .
P02.118
chromosomal translocations in couples with recurrent
miscarriage - a retrospective study
C. Gug 1 , I. Cioata 1 , A. Cretu 1 , G. Budau 1 , M. Cartis 1 , L. Stelea 1 , F. Dorneanu 1 ,
M. Munteanu 1 , D. Hutanu 1 , N. Milos 1 , L. Sabau 2 ;
1 University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania,
2 University of Oradea, Faculty of Medicine and Pharmacy, Oradea, Romania.
Studies have shown that couples with reproductive loss have a high
frequency regarding chromosomal translocations (of 3% for females
and 2% for males) . This study presents the results of conventional cytogenetic
analysis in 700 couples referred to our genetic center . Chromosomal
analyses were performed using Giemsa-banding according
to standard procedure on peripheral lymphocytes . Each couple has
received genetic counseling. Translocations have been identified in 23
cases, 11 in male patients and 12 in female patients . Two Robertsonian
translocations trob(13;14) have been found in male patients, in different
families and 5 types of balanced translocations, on a number of 9
male patients: t(2;21)(q34;p11 .2) one case, t(4;16)(q34;q24) one case,
t(2;17)(p22;q21) one case, t(7;15)(q14;q27) one case, t(7;14) one
case, t(7;18)(p13;q11) one case, t(1;5)(q23;p12) three cases in one
family. In women patients, we have identified one case of Robertsonian
translocation, trob(13;22), and 9 different types of balanced transloca-