2009 Vienna - European Society of Human Genetics

Cytogenetics
Metaphase chromosomes were prepared using standard cytogenetic
methods. Chromosomes were analysed by using RHG banding and
karyotypes were interpreted according to ISCN 1995 nomenclature.
The mean patient age was 28 years.
An overall frequency of 16,94 % chromosomal abnormalities was detected
for our 65 patients. Sex chromosome abnormalities were predominant
(90% of cases).
Among primary amenorrhea women, 16 had a 46,XX karyotype and
5 (26.3%) had abnormal karyotype: 45,X /46,XX , 46,X idic(X)(q11),
46,X,del(X)(q 21), 46,XY and 45,X /46,XY.
Karyotypes of patients with secondary amenorrhea were abnormal in
5 cases (12,5%) including four X chromosome mosaicism and one
autosomal translocation: 45, X /46,XX , 46,XX /47,XXX, 45X/47,XXX
and 46,XX, t(12 ;19) (q13 ;q13).
The present study has emphasized that karyotyping is one of the fundamental
investigations in the evaluation of amenorrhea. Cytogenetic
abnormalities seem to be more frequent in primary than secondary
amenorrhea and mainly involve the X chromosome. Women with different
cytogenetic types of X chromosome abnormalities should be diagnosed
at young age and beneficiate of a carefully followed throughout
life.
Genetic counseling is very hard for these patients but mutational analysis
of candidate genes in 46,XX idiopathic amenorrhea is needed to
determine which genes contribute to the cause of this disorder.
P03.006
molecular neurocytogenetic survey of variations in chromosome
numbers and arrangement in the schizophrenia brain
Y. B. Yurov 1,2 , I. Y. Iourov 1,2 , S. G. Vorsanova 1,2 , A. K. Beresheva 2 , I. A. Demidova
2 , A. D. Kolotii 2 , V. S. Kravets 2 , V. V. Monakhov 1 , I. V. Soloviev 1 , V. M.
Vostrikov 1 , T. Liehr 3 ;
1 National Research Center of Mental Health, RAMS, Moscow, Russian Federation,
2 Institute of Pediatrics and Children Surgery, Rosmedtechnologii, Moscow,
Russian Federation, 3 Institute of Human Genetics and Anthropology, Jena,
Germany.
It has been proposed that alteration of genome organization and behavior
in neuronal cells could contribute to schizophrenia pathogenesis.
However, related studies rarely address genomic variations at
subchromosomal and chromosomal levels in the diseased brain. We
have addressed variation in chromosome numbers and somatic chromosome
pairing in neural cells of the schizophrenia brain by interphase
FISH. We demonstrate that the schizophrenia brain exhibits increased
rates of stochastic aneuploidy affecting different chromosomes with
the presence of low-level mosaicism involving chromosomes 1, 18,
21 and X. Variation in chromosome number may destabilize grnome
in affected neuronal cells and play a definite role in schizophrenia
pathogenesis. The study of interphase chromosome organization has
showed the schizophrenic brain to differ in the rate of chromosomal
associations by both heterochromatic and euchromatic regions. The
frequency of somatically paired heterochromatic regions was 1.5-3
times higher for chromosomes 1, 9, 16 and 18 and for euchromatic
regions of chromosomes 1 and 18, while pairing of chromosomes 15
and 17 has occurred more frequently in the non-diseased brain. Since
nuclear organization defines proper functioning of a cell, the present
findings propose for the first time alterations of chromosome organization
in the brain as a possible epigenetic mechanism involved in the
pathogenesis of schizophrenia. In summary, we can conclude that the
schizophrenia brain is hallmarked by specific behavior of neuronal genome
which probably defines the cellular pathobiology of this common
psychiatric disease. Supported partially by Philip Morris USA.
P03.007
comparative analysis of numerical and structural chromosome
aberrations in peripheral blood lymphocytes from workers upon
exposure to plutonium-239
V. A. Timoshevsky, I. N. Lebedev, V. A. Vasilyev, N. N. Sukhanova;
Institute of medical genetics, Russian academy of medical sciences, Tomsk,
Russian Federation.
Aneugenic mechanisms of activity for ionizing radiation have been
debated for some time while its genotoxic and clastogenic action is
well known. Six human chromosomes were investigated in pairs (2
and 8, 7 and 12, X and Y) for the purpose of comparative estimation
of non-disjunction and lagging frequency in the binucleated human
lymphocytes from workers of nuclear-chemical industry and clinically
healthy men of the same age using dual-color fluorescent in situ hybridization.
In addition spectrum and level of structural chromosome
aberration were estimated by G-banding technique. Statistically significant
increasing of non-disjunction frequency has been found for all
investigated autosomes in the cells of exposed individuals in comparison
with controls. There were no differences between groups in the
frequencies of gonosome non-disjunction. Chromosomal loss, which
was detected as centromeric positive micronuclei, demonstrated no
differences also. Analysis of the G-banded metaphase spreads has
indicated that the main distinction between exposed and unexposed
individuals was composed of the chromosomal aberrations such as
deletions and translocations, which failed to be finding using conventional
solid-stained analysis. Thereby the internal exposure high-LET
alpha-particle irradiation demonstrates aneugenic activity along with
clastogenic effect, that can be result both alteration metaphase spindle
and abnormal segregation of the rearranged chromosomes. So, it is
advisable in the course of genotoxic investigations to use the analysis
of aneugenic effects in addition to standard approaches. Using binucleated
human lymphocytes coupled with FISH for non-disjunction
assessment proved to be the most sensitive technique for detection
of aneuploidy.
P03.008
characterization by FisH and array-cGH of 26 apparently
balanced chromosomal rearrangements associated with an
abnormal phenotype
F. Petit 1 , B. Duban-Bedu 2 , O. Boute-Bénéjean 1 , M. Holder-Espinasse 1 , J. Cuisset
1 , S. Sukno 2 , S. Manouvrier-Hanu 1 , J. Andrieux 1 , B. Delobel 2 ;
1 CHRU de Lille, Lille, France, 2 GHICL, Lille, France.
Apparently balanced chromosomal anomalies affect around 0.5% of
individuals. Regarding de novo reciprocal translocations, inversions
and complex chromosomal rearrangements (CCR), mental retardation
and/or congenital malformations are more frequent compared to the
general population. We report 26 patients presenting abnormal phenotypes
and chromosomal rearrangements considered balanced by
conventional cytogenetics (20 reciprocal translocations of which one
X-autosome, 5 inversions and 1 CCR), de novo (n=18) or inherited
(n=8). All were analysed by oligonucleotide array-CGH: 8 turned out to
be unbalanced, representing 25% of inherited cases, and 35% of de
novo cases. All cryptic imbalances were deletions, ranging from 1 to
15 Mb, of which 2 were localized at distance from the breakpoints. For
the remaining 18 patients, no quantitative anomaly was detected at
150 kb resolution. Few of them were selected to characterize precisely
the breakpoints by FISH. Gene breakage was identified in two of them.
In one case, a new gene implicated in facial clefts namely FAF1 was
identified. In the other case, disruption of DMD gene was revealed in a
girl presenting a progressive dystrophinopathy. According to previous
studies, although these are preliminary results, two major pathogenic
mechanisms are underlined in this context: cryptic deletions and gene
disruption. This suggests that array-CGH must be performed systematically
when apparently balanced chromosomal rearrangement is associated
with an abnormal phenotype, including during pregnancy.
P03.009
cytogenetic changes of individuals occupationally exposed with
arsenic
A. Karthick Kumar, V. Balachandar, M. Arun, P. Manikantan, S. Mohanadevi,
K. Sasikala;
Bharathiar University, Coimbatore, India.
Long-term exposure to inorganic arsenic from various factor has been
documented to induce cancers and vascular diseases in a dose response
relationship. Arsenic levels in urine, hair, and nail are biomarkers
for short-term internal dose, skin hyperpigmentation and palmoplantar
hyperkeratosis are for long-term (many years) internal dose,
and percentage of monomethylarsonic acid in total metabolites of inorganic
arsenic in urine may be considered as an exposure marker for
biologically effective dose. The biomarkers of early biological effects of
ingested inorganic arsenic included blood levels of reactive oxidants
and anti-oxidant capacity, genetic expression of inflammatory molecules,
as well as cytogenetic changes of peripheral lymphocytes. In
this regard present study find out whether the arsenic induced genetic
damage or not in peripheral blood lymphocytes in exposed subjects. By
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