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

Cytogenetics
P0302. Cytogenetic analysis of the human genome reactivity to
the potentially mutagen environment represented by ionizing
radiation
D. Usurelu, D. Cimponeriu, P. Apostol, I. Radu, L. Gavrila;
Institute of Genetics - University of Bucharest, Bucharest, Romania.
One of the most important mutagen agents in developing different
types of cancer is the ionizing radiation. So, in this study, we are focusing
our analysis on persons who are working in a potentially mutagen
environment (near an accelerator for ionizing radiation).
We’ve analyzed twelve persons (one control and ten workers) by classical
cytogenetic technique and by FISH.
After the cytogenetic analysis we’ve determined that there were not
any important chromosomal modifications, the only one present being
PCDs (premature centromere division) with a frequency of 5 -11%.
Counting on the fact that the PCDs was present even in the control in
2 % frequency and in the field literature being considered normal to
have 7-8% of PCDs, we have concluded that the percentage we’ve
obtained for that subjects is normal and it is not due to the effect of the
working environment.
The most important targets for ionizing radiation being the telomeres,
we’ve tested from this point of view on our subjects the eventual effect
of radiation, presumptive to be in the environment, by FISH technique.
Comparing the frequency of the telomeric signals obtained from the
control (98%-100 %/metaphase) to those from that subjects (91%-
96%/metaphase), we found that the differences can not be considered
significant.
Corroborating the obtained data, we can conclude that for our eleven
analyzed subjects there are not obvious chromosomal modification determined
by fact that they are working with a radiation source.
P0303. Frequency of mosaic aneuploidy in children with
idiopathic autism
Y. B. Yurov 1,2 , S. G. Vorsanova 2,1 , I. Y. Iourov 1,2 , I. A. Demidova 2 , A. K. Beresheva
2 , V. S. Kravets 2 , V. V. Monakhov 1 , A. D. Kolotii 2 , V. Y. Voinova-Ulas 2 , N. L.
Gorbachevskaya 1 ;
1 National Research Center of Mental Health, RAMS, Moscow, Russian Federation,
2 Institute of Pediatrics and Children Surgery, Roszdrav, Moscow, Russian
Federation.
It has been repeatedly suggested that numerous human diseases including
major psychiatric disorders could be associated with mosaic
aneuploidy. Here, we have attempted to test this hypothesis concerning
autism, a common childhood psychiatric disorder. About 5-10% of
autism cases are known to be caused by chromosomal abnormalities
or gene mutations. However, mosaic aneuploidy in autism has not ever
been studied. We surveyed stochastic aneuploidy in children with/without
idiopathic autism by interphase multiprobe fluorescence in situ hybridization
(mFISH). The rate of chromosome loss and gain involving
six arbitrarily selected autosomes (chromosomes 1, 9, 15, 16, 17, 18)
and sex chromosomes was assessed in peripheral blood cells of 60
unaffected male children and 116 male children with idiopathic autism.
Studying over 420,000 cells, we have determined the mean frequency
of stochastic aneuploidy in control and autism:
Control Chromosome loss Chromosome gain
Autosomes
Sex chromosomes
Autism
Autosomes
Sex chromosomes
0.58% (95% CI 0.42-0.75%)
_
0.60% (95% CI 0.37-0.83%)
_
0.15% (95% CI 0.09-0.21%)
1.11% (95% CI 0.90-1.31%)
0.22% (95% CI 0.14-0.30%)
1.01% (95% CI 0.85-1.17%)
CI - confidence interval
The difference of stochastic aneuploidy rate was insignificant. However, the frequency
of mosaic aneuploidy over the background level was found in 19 (16%) of 116 children
with idiopathic autism, while outlier values were not found in controls. These data
identify mosaic aneuploidy as a new autism genetic risk factor. Therefore, molecular
cytogenetic analysis of somatic mosaicism is warranted in children with idiopathic autism.
Supported by INTAS and RGNF (060600639a).
102
P0304. Cytogenetic examination of healthy individuals for the
assessment of their individual sensitivity to ionizing radiation
N. Ryabchenko, E. Dyomina;
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
of National Academy, Kyiv, Ukraine.
The increased level of chromosomal abnormalities in somatic cells is
proposed as the marker of increased cancer risk. Recent reports have
suggested that elevated chromosome aberration yields observed following
irradiation of peripheral lymphocytes in G 2 phase of cell cycle
caused by the impaired DNA repair and hereditary predisposition to
cancer.
G 2 assay is based on high chromosomal sensitivity of human peripheral
blood lymphocytes to radiation. Examination of 103 relatively
healthy individuals was carried out by means of the adopted G 2 -assay
consisting in the analysis of radiation induced cytogenetic effects in
peripheral blood lymphocytes in the most radiosensitive post-synthetic
phase of cell cycle. The dose of test gamma-irradiation of cell cultures
was 1,5 Gy.
The obtained cytogenetic parameters induced by the test irradiation
in G 2 -phase of cell cycle revealed high interindividual variability: 0,18 -
1,24 aberrations/metaphase, with mean value - 0,410,10; coefficient of
variation (CV) - 24%. Chromatid breaks prevailed in aberration spectra
up to 98% with mean 0,370,097, CV = 27%. Analysis of the character
of chromatid aberrations distribution made it possible to reveal 12%
(12/103) individuals with increased chromosomal radiosensitivity. Indications,
which reflect the prime contingent for cytogenetic assessment
of individual radiosensitivity, were carried out.
Taking into account connection between the radiation induced high
levels of chromosomal aberrations, genome instability and the tendency
toward increased risk of cancer, individuals with high values of
chromosomal radiosensitivity can be related to the group of potentially
increased radiation and cancerogenic risk who require thorough medical
and cytogenetical monitoring.
P0305. Clinical findings in a patient with interstitial deletion 1q31
and two patients with terminal deletion 1q syndrome
E. Karaca, S. Başaran Yılmaz, U. Yanar, B. Bağlama, B. Tüysüz;
Istanbul University, Cerrahpasa Medical School, Medical Genetics, İstanbul,
Turkey.
We report 3 cases of de novo 1q deletion. The first case is 3 years 6/12
months old child that has a story of IUGR. His language and social
developmant was delayed but gross motor skill was normal and he had
microcephaly, fine and sparse hair, sparseness on medial parts of eyebrows,
flat-high forehead, broad nasal root, short nose, low-posterior
set ears, simian crease on his left hand, clinodactyly and micropenis.
His weight, height and head circumference were under 3. centile. An
accessory spleen found in abdomen USG. Karyotype analysis showed
46,XY, del (1)(q25.3-q31.3). Second and thirth cases are 3 years and
4 years 7/12 months old of males. They both have a story of SGA
and clinical features of hyperactivity, severe neuromotor and mental
retardation, fine-sparse hair, microcephaly, epicanthus, hypertelorism,
depressed nose root, hipospadias and seizures The second case also
has prominent glabella, pseudostrabismus, big ears, cryptorchidism
and his MRI shows agenesia of corpus callosum. The thirth case was
referred us with the complaint of frequent pulmoner enfections with
cellular immune deficiency and atypic face that consists of full cheek,
microretrognathia apart from the second. These cases karyotype analysis
revelaed 46,XY, del (1) (q42.2-qter). In conclusion; our first case
has similar features with two other cases of 1q31 deletion reported in
the literature, however, motor development was normal. Second and
thirth cases each have the characteristic features of del 1(q42-qter)
patients reported before as hipospadias, severe motor-mental retardation,
seizures, depressed nose root, fine-sparse hair and agenesia of
corpus callosum.