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

Cytogenetics
provided for every case.
In conclusion, we present 5 different chromosomal abnormalities involving
chromosome 5 in order to discuss variability of clinical features
and management protocol.
P0311. Structural chromosome abnormalities and male fertility
E. M. Grishina, L. F. Kurilo, T. M. Sorokina, L. V. Shileiko, V. B. Chernykh;
Research Centre for Medical Genetics of Russian Academy of Medical Sciences,
Moscow, Russian Federation.
The aim of this study is to evaluate the prevalence of structural chromosome
abnormalities in infertile men and to assess their effect on the
spermatogenesis and male fertility.
The examined cohort consisted of 550 men from infertile couples. The
semen analysis has been performed according to the WHO recommendations
(1999). According to the sperm tests all patients were
subdivided into five groups: azoospermia (n=177), oligozoospermia
(n=203), asthenozoospermia (n=81), teratozoospermia (n=39), and
normozoospermia (n=50). Chromosome analysis has been carried out
on peripheral lymphocytes using standard cytogenetic techniques with
GTG- and C- staining.
In 3.1% examined men structural chromosome abnormalities have
been found. The translocations have been found in 16 patients, and
pericentric inversion of chromosome 5 - in one azoospermic patient.
In 53% cases the chromosome rearrangements are Robertson translocations.
Most commonly chromosome translocations between chromosomes
13 and 14 were found.
Chromosome aberrations have been found in 1.7% azoospermic,
4.4% oligozoospermic, 2.6% teratozoospermic, 3.7% asthenozoospermic,
and 2.0% normozoospermic men. Between patients with revealed
chromosome abnormalities the azoospermia has been diagnosed in
17.6%, oligozoospermia - 52.9%, asthenozoospermia - 17.6%, teratozoospermia
- 5.9%, and normozoospermia - in 5.9% cases.
Our results have demonstrated obvious polymorphism of status of
sperm parameters in men with structural chromosome abnormalities.
In most infertile men the chromosome translocations associated with
oligozoospermia.
P0312. Molecular characterization of terminal Xp deletions by
m-Banding and Array-CGH in four families
C. Leroy1 , E. Landais1 , V. Sulmont2 , A. Hecart3 , H. Grulet3 , N. Michel1 , N. Gruson1
, S. Clomes1 , M. Mozelle1 , J. Motte2 , D. Gaillard1 , M. Doco-Fenzy1 ;
1Service de Génétique, CHU Reims UFR Médecine IFR53, Reims, France,
2Service de Pédiatrie, American Memorial Hospital, CHU Reims, Reims,
France, 3Service d’Endocrinologie, CHU Reims, Reims, France.
Xp deletions are diagnosed in about 6% of Turner stigmata. The phenotype
is probably associated with haploinsufficiency of genes within
the deleted regions but the correlation between the length of the deletion
and the phenotype is still unknown.
We studied the length of the terminal Xp deletion through four families.
We report here the phenotypic and laboratory findings in 8 female
members affected by the Xp deletion. The deletions were diagnosed
cytogenetically using 400 band R and G-Banding, X specific mBanding
and were further delineated by array comparative genomic hybridisation
(array-CGH). We used a 1 Mb BAC and PAC array (VIB Leuven),
DNAs were tested by experiment using a triangle testing with
control DNAs. Data were analysed with the arrayCGHbase software
(J.Vermeesch).
Results:
Cytogenetic studies showed the following breakpoints: del(X)(p22.2),
del(X)(p21.3), del(X)(p11.4), der(X)(qter->p22.2::q22->qter) in families
1,2,3 and 4 respectively.
Array-CGH established the length of the Xp deletions: 7.5 Mb, 20.3
Mb, 24.2 Mb, 9.5 Mb in families 1,2,3 and 4 respectively.
None of the 8 female patients had mental retardation. Their common
feature was short stature when present (height: 1.40m to 1.64m in
adults). Interestingly SHOX region was deleted in all of them. Array-
CGH enabled a comparison of each genotype-phenotype association.
An important interindividual and intrafamilial variability was observed,
caused by parameters such as X inactivation bias, or specific gene deletion
or disruption. Our data showed no correlation between the adult
height and the deletion length and may contribute to the evaluation of
GH treatment when proposed.
Grant: PHRC-2005-CHU-Reims.
10
P0313. Molecular characterization of chromosome Y structural
abnormalities in two cases of ambiguous genitalia
A. G. Lungeanu 1 , A. A. Arghir 1 , S. Arps 2 , G. M. Cardos 1 , N. Dumitriu 3 , A. Rodewald
4 ;
1 ”Victor Babes” National Institute, Bucharest, Romania, 2 GeneteQ, Hamburg,
Germany, 3 Children Hospital “Marie Curie”, Bucharest, Romania, 4 Institute for
Human Biology, Hamburg, Germany.
Malformations of the external and/or internal genitalia may be caused
by structural abnormalities of sex chromosomes.
With the aim to understand the underlying cause of ambiguous genitalia,
and to contribute at management of the patients with abnormal
phenotypic sex, we investigated two cases using GTG, CBG banding,
accomplished by FISH and PCR techniques.
FISH included: DAPI stain, Y-specific painting probe XCP-Y ( Meta-
Systems), Ycen DYZ3, Yq12 DYZ1, Yp11.3 SRY, Xcen DXZ1 (Vysis),
subtelomeric probes for X- and Y-chromosome, locus DXYS130 and
DXYS224 (Q-Biogene). PCR method was performed with a short DNA
sequence from Amelogenine gene on the short arm of both X and Y
chromosomes (Xp22.31-p22.1, Yp11.2), plus DYS392 STR marker
(Yq11.2).
GTG banding showed mosaic karyotypes in both patients: 45,X[84]/
46,X idic(Y)(qter--pter::pter--qter)
[16], and 45,X[65]/46,X idic?(Yp)[35], respectively. By CBG banding
the provenience of idic(Y)(pter--qter) it was clear in the first case, but
difficult in the second one. By FISH, the karyotype was:
1).46,X,psu idic(Y)(p11?.2).ish psuidic(Y)(qter--pter::pter--qter)(wcpY
+,DXYS130++,SRY++,DYZ3++.
DYZ1++,DYS224++). PCR revealed both Amelogenine gene sequence
and DSY392 marker.
So, it was confirmed that abnormal Y is an isodicentric with breakpoint
distal from subtelomeric locus DXY130 in Yp.
2). FISH karyotype was: 46,X,?idic(Y)(q11).ish idic(Y)(pter--q11::q11-
-pter)(SRY++). PCR revealed Amelogenine gene sequence, but not
DSY392 marker so, the fusion point is in the long arm Yq11.
By our results we can conclude that, various shapes of structural abnormalities
in Y chromosome may result in disorders of sex determination
pathway which are poorly understood. Only the presence of SRY
gene is not enough for male phenotypic normality.
P0314. Cytogenetic diagnosis of chromosomal pathology in
various stages of pregnancy
G. J. Abildinova, G. S. Svaytova, K. A. Koshkarova, A. G. Baysbekova, N. Z.
Musachanova;
The centre of molecular medicine, Almaty, Kazakhstan.
The detection of chromosomal anomalies is one of the main tasks in
prenatal diagnostics. It is known, that the majority chromsome abnormalities
result fetal death or the birth of children with handicaps. We
studied fetal karyotypes in a group of high-risk pregnancies.
Materials and methods of research. In total we analyzed chorion villus
and fetal blood of 879 pregnant women in various terms of pregnancy.
The preparations of chromosomes were prepared from chorion villus
by direct culture. For preparation of preparations from fetal blood used
standard methods with addition PHA.
Results of research and discussion. The analysis cytogenetically of
results has shown, that in among chromosomal abnormalities, numerical
anomalies prevailed. In 53,3 % cases Down’s syndrome was diagnosed
- 47, XY +21, both complete and mosaic forms. In 3,3 % cases
we diagnosed Patau syndrome - (47, XY+13). In 25,9 % cases we detected
marker chromosomes. Besides numerical changes we detected
structural changes in 10 % cases: Robertsonian translocation - 45,
t(15;21), 46,isoX(q) and a reciprocal translocation - 45, t(3;Y).
P0315. Detection of mixed chimerism and minimal residual
disease after bone marrow transplantation in chronic myeloid
leukemia by conventional and molecular cytogenetics in
tunisian patients
F. Talmoudi 1 , M. Ben Rekaya 1 , F. Boumaiza 1 , T. Ben Othman 2 , A. Amouri 1 ;
1 Cytogenetic Laboratory, Tunis, Tunisia, 2 CNGMO, Tunis, Tunisia.
Chronic Myeloid Leukemia (CML) is an hematopoietic malignancy
characterized by the proliferation of myeloid precursors. The hallmark
of CML is the presence of Philadelphia (Ph 1 ) chromosome that results
from balanced reciprocal translocation between chromosomes 9 and