2008 Barcelona - European Society of Human Genetics

Cytogenetics
aimed at identifying the frequency of chromosomal aberrations among
children with epilepsy . Methods: Twenty Egyptian children with epilepsy
were recruited for this study . Full history, clinical & neurological
examination together with some investigations (EEG, MRI & CAT) was
done . Chromosomal analysis using GTG banding and high resolution
techniques were evaluated, FISH technique was done to one case
only . Results: Chromosomal aberrations were observed in 3/20 (15%)
of which one case had mosaic interstitial deletion 15(q11q13), the second
case had mosaic inversion 22(q11q13), While the third case had a
ring of chromosome 18 . Conclusions : The possibility of chromosomal
abnormality in cases of epilepsy without apparent etiology and / or associated
congenital malformation or witout frank dysmorphic features
should be seriously acknowledged . Genetic evaluation including high
resolution chromosomal study, FISH technique and molecular study
should be used for proper management and counseling .
P02.147
induced chromosomal breakage rate in children referred for
aplastic anemia
N. Selenti, A. Kolialexi, E. Kouvidi, H. Fryssira, S. Kitsiou, V. Touliatou, E.
Kanavakis, A. Mavrou;
Medical Genetics Athens University School of Medicine, Athens, Greece.
Background: Fanconi Anemia (FA) is a rare autosomal instability syndrome
characterized by bone marrow failure, developmental anomalies,
acute nonlympocytic leukaemia and cellular hypersensitivity to
cross linking agents such as diepoxybutane (DEB) and mitomycin C
(MMC) . However, a number of patients display only minor phenotypic
variations or lack congenital anomalies .
Material & Methods: Chromosomal breakage analysis using MMC and
DEB was performed to differentiate FA from aplastic anemia in 166
children aged from 2 months to 14 years with myelodysplasia with or
without congenital malformations . Matched for age and sex donors
were used as controls . Peripheral blood samples were analysed with
conventional cytogenetic techniques . For clastogen-induced chromosome
damage both MMC and DEB were added . A minimum of 150
metaphases per case were analyzed . FA positive was concidered the
case in which the percentage of breaks was 7-10 times higher as compared
to controls .
Results: Incuced breaks were detected in 8/166 patients tested with
both clustogens . Six were diagnosed as FA while the remaining two,
despite the high percentage of clastogenic damage, were characterised
as Silver Russell syndrome and Blackfan Diamond anemia respectively
. 3/6 FA patients presented with congenital anomalies and
3 only with aplastic anemia . 2/6 FA patients were dizygote twins . No
relationship was found between the clinical severity of the disease,
age of onset, and the anemic status .
Conclusions:The present study illustrates that clustogens induced
stress tests provide the means of differentiation between FA and
«aplastic anemia» and allow for accurate and timely diagnosis to implement
appropriate therapy .
P02.148
molecular cytogenetic characterization of the same translocation
in two siblings
T. V. Zolotukhina 1 , N. V. Shilova 1 , N. B. Rubtsov 2 , T. Karamysheva 1 , Z. G.
Markova 1 , V. A. Galkina 1 , T. G. Tsvetkova 1 ;
1 Research Centre for Medical Genetics of RAMS, Moscow, Russian Federation,
2 Institute of Cytology and Genetics SB RAS, Novosibirsk, Russian Federation.
We are reporting the clinical, molecular cytogenetic studies of two female
siblings of 14 and 6 years, who was refferred for karyotyping
because of multiple congenital anomalies and mental retardation . The
karyotypes of parents were normal . Phenotypes of proband were similar
and included: spine deformaty, mild microcephaly, large nose with high
nasal bridge, micrognatia and crowded teeth . Conventional cytogenetic
analysis of both siblings using GTG-banding revealed 46, XX,der
(15) karyotype . FISH analysis with mFISH probe kit (MetaSystems),
wcp15, wcp 8, telomere specific for chromosome 8 DNA-probes (Abbott)
was performed to identify derivate chromosome . mFISH showed
the origin of the material from the chromosomes 8 and 15 . FISH with
wcp15, wcp 8 confirmed this date and 8q telomere was seen on the
derivate chromosome . Thus the derivate chromosome was composed
from the part of long arm of chromosome 8 and whole chromosome
15 . For detailed karyotype description DNA probes were generated
from abnormal chromosomes followed with DOP-PCR and labeling of
PCR products in additional cycles of PCR . In patients FISH of these
microdissected DNA probes painted abnormal chromosome 15(p11 .2qter)
and 8(q22 .1-qter) . In healthy donors they painted 15(p11 .2- qter)
and 8(q22 .1-qter) . Technique of M-bands with DNA probes derived
from two different mar(15) revealed no additional reorganization in
pericentromeric region of abnormal chromosomes . Obtained data allowed
us to described abnormal karyotypes as 46, XX, der(15)t(8;15)(
q22 .1;p11 .2) .The normal karyotypes of both parents led us to hypothesis
that this der(15) is probably a result of parental gonadal mosaicism .
Different biological father cannot be excluded
P02.149
MCA/MR Syndrome with (4; 10) (q25; q26) Translocation
A. A. Dardir, H. A. Hussein, N. A. Meguid;
National Research Center, Cairo, Egypt.
We describe a 52 days boy with low birth weight, sparse scalp hair,
absent eye brows and eye lashes and bilateral corneal opacities, umbilical
hernia and anal stenosis . Limb anomalies in the form of bilateral
syndactyly between first, second and third fingers, bilateral lower limb
preaxial polysyndactyly and bilateral soft tissue syndactyly between
second and third toes are described . The karyotype of the infant revealed
a unique de novo translocation involving chromosomes 4 and
10, which was confirmed by Fluorescence In Situ Hybridization (FISH)
technique, resulting in t(4;10)(q25;q26) . No other patients, to our knowledge,
with an identical phenotype and chromosomal finding have been
reported . Our report suggests that regions 4q25 and 10q26 may be
involved in the development of the limb anomalies, eye anomalies and
other characteristic clinical findings presented in our patient.
P02.150
Detecting of gonadal mosaicism for trisomy of chromosomes
without severe imprinting effects
M. Tahmasebi-Hesari, N. V. Kovaleva;
St. Petersburg Medical Academy of Postgraduate Studies, St. Petersburg, Russian
Federation.
Gonadal mosaicism (GM) may account for both recurrent cases of
chromosomal anomalies and appreciable proportion of “sporadic” cases
. However even in the case of a recurrent anomaly, it is not always
easy to discover a suspected GM in the absence of the abnormal line
in a somatic tissue of a carrier . To optimize the testing procedure, we
have conceived the following algorithm . (i) Study on parental origin
of the extra chromosome in the trisomic offspring . (ii) Finding apparent
non-disjunction (NDJ) is followed by testing the grandparents on
the parent-of-origin’s side . Presence of two homologs from the same
grandparent in the parent-of-origin (uniparental disomy, UPD) and in
the trisomic proband, would indicate GM in the parent-of-origin . (iii)
Finding a “new” extra chromosome in the proband is followed by testing
the grandparents on both sides . Presence of a grandparental homolog
not seen in both parents in the proband, would uncover a carrier
of GM . Presence of crossovers (“new” allele) may add to uncovering
both GM and its carrier . Finding UPD or a “new” chromosome/allele in
a healthy offspring may also help to reveal the presence of GM in a
parent . (iv) Parents-of-origin with undetectable GM should receive a
rigorous multi-tissue cytogenetic investigation for the presence of abnormal
line . We believe that expenses of labour- and time-consuming
testing of families for suspected GM can be rewarded by the opportunity
of choosing a desirable reproduction strategy . Results of a pilot
study of 30 families with trisomy 21 offspring will be presented .
P02.151
Karyotyping of early passaged human mesenchymal stem cells
J. Shalygina 1 , A. Pendina 2 , O. Efimova 1 , T. Kuznetsova 2 , P. Kruglyakov 3 , E.
Shvedova 3 , D. Polyntsev 3 , V. Baranov 2 ;
1 Saint-Petersburg State University, Saint-Petersburg, Russian Federation, 2 D.O.
Ott’s Institute of Obstetrics & Gynecology RAMS, Saint-Petersburg, Russian
Federation, 3 Transtechnologies Ltd., Saint-Petersburg, Russian Federation.
Human mesenchymal stem cells (hMSC) have a great potential for
a wide range of therapeutic purposes . Their medical application necessarily
requires preliminary passaging . The question of unfavorable
effects of passaging of hMSC on their genome (chromosome) stability
remains controversial .
We have studied genome stability of hMSC, obtained from 6 healthy