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

Cytogenetics
P0394. Evaluation of the recurrent miscarriage by chromosome’s
analysis in the Cytogenetic Laboratory of the Clinic Obstetric-
Gynecology Hospital “Dr. Dumitru Popescu” Timisoara
M. Mihaescu 1,2 , D. Navolan 3,4 , E. Taurescu 3,4 , C. Citu 3,4 , I. Sas 5 , D. Chiriac 5 , D.
Citu 3,4 ;
1 University of Medicine and Pharmacy “Victor Babes”, TIMISOARA, Romania,
2 Cl. Hosp. Ob-Gyn”dr. Dumitru Popescu”- Cytogenetic Laboratory, Timisoara,
Romania, 3 University of Medicine and Pharmacy, TIMISOARA, Romania, 4 Cl
Hosp Ob-Gyn”dr. Dumitru Popescu”, Timisoara, Romania, 5 Cl. Hosp Ob-Gyn,
TIMISOARA, Romania.
Due to the age of the future parents, the consensus on the moment
of evaluation of a recurrent miscarriage has changed from after third
or fourth to after second miscarriages. Chromosomal anomalies are
known as one of the common causes of the spontaneous abortion.
The problem identification and the diagnostic procedures include a
large sample of practices: cytogenetic studies, studies regarding the
anatomic integrity of the genital organs, studies concerning the diagnosis
of the endocrine abnormalities, and the assessment of the blood
coagulation protein/platelet defects.
In the Cytogenetic Laboratory of the Clinic Obstetric-Gynecology Hospital
“Dr. Dumitru Popescu”, founded in March, 2006, the chromosome
imbalance can be diagnosed by cytogenetic investigations of virtually
any tissue type. The cytogenetic studies of abortuses (7 cases), were
carried on using entire abortus (2 cases), placental villi (2 cases), amnion
(2 cases), and, for the first time in our country, fetal biopsy (3
cases). For advanced gestation, the fetus’ blood in a sodium heparin
was also utilized (2 cases). The culture success rate was increased
by using more sample types for the same case (4 cases). The used
culture techniques - fibroblast cultures, amnion cultures, placental villi
cultures, blood cultures - were standardized and their processing was
done according to the standard protocols. The chromosomes analysis
was carried on (Ikaros-Metasystem) after the GTG banding. We also
analyzed, during the same period, blood samples of 10 couples with 2
or more spontaneous abortions.
Results: aneuploidies (2 cases 45, X, and loss of various chromosomes),
2 cases of normal karyotype and 3 cases of culture failure.
Among the couples we found 1 balanced translocation t(4;15), 1 case
inv 9 (p12;q13) and normal karyotype for the rest.
P0395. Chromosome Abnormalities (ChrA) detected by
conventional and high resolution (HR) cytogenetic assessment
in tumor cells (TuC) and blood lymphocytes (BLy) from 18
patients with renal cell carcinoma (RCC)
A. B. Falcón de Vargas1,2 , R. E. Vargas Arenas1 , H. Dávila1 , M. Uribe1 , M.
Seemann1 ;
1 2 HCC-Institute of Inmunology, Caracas, Venezuela, Genetics Unit, Vargas
Medical School. Faculty of Medicine, UCV., Caracas, Venezuela.
In 18 patients with diagnosis of RCC, 10 males and 8 females, mean
age 59.9+/-11.2 years (range: 17 to 74), conventional and HR studies
were carried out in Chr from TuC and BLy. A total of 322 metaphases
in TuC and 534 in BLy of patients and 534 in BLy of 18 healthy controls
matched by age and sex were studied. Results showed numerical and
structural changes of Chr in patients with RCC (p 60 (12/1), endoreduplications (6/2),
double minute (6/2), dicentrics (3/0), triradios (3/0), quadriradios (3/0).
Numerical clonal changes: +7 in 4/1, +7+7 (2/0), +7+8 (1/0), +8 (7/0),
+10 (5/2), +11 (1/0), +13 (1/0), -3 (1/0) , -8 in 1/0, -10 (2/0), -X (2/0), -Y
(4/3). A translocation t(3;8) (3p14.2-8q24) was found in TUC of one patient;
deletion del 3p14 and a complex reorganization were also found
in one patient in each case.
We conclude that ChrA are present in a high proportion of TuC and in
a lower proportion in BLy of patients with RCC. These ChrA should be
considered inespecific since could be seen in other conditions such as
different types of cancer, hematooncological disorders and virus infections,
and also induced by mutagenic agents.
Further studies are required to determined the clinical value of these
changes from the prognosis and therapeutic viewpoint in RCC.
122
P0396. Subtelomere rearrangements in couples with repeated
miscarriages
E. Morizio 1 , C. Nuzzi 2 , P. Guanciali-Franchi 1,2 , D. Romagno 1 , G. Calabrese 1,2,3 ,
G. Palka 1,2,3 ;
1 Genetica Medica, Pescara Hospital, Pescara, Italy, 2 Genetica Medica, University
of Chieti, Chieti Scalo, Italy, 3 G. D’Annunzio Foundation, Chieti Scalo, Italy.
Subtelomeric rearrangements, currently detected by FISH, STR, MLPA
or Array-CGH approaches, are known to be associated with mental
retardation and congenital malformations. Few reports describe subtelomere
rearrangements in women with repeated miscarriages. By
FISH analysis with a complete panel of subtelomere probes (Cytocell,
UK; Vysis, USA; MP, France) we investigated 60 couples suffering
for recurrent abortions (>2 aborted foetuses). All couples had normal
karyotype and no clinical or genetic anomalies. In 2 couples (3%) we
identified a subtelomeric rearrangement. In a couple referred for four
consecutive 1st trimester spontaneous abortions, the spouse, nullipara,
had a reciprocal translocation t(9;16)(q34;p13.3) de novo. In
another couple with three 1st trimester spontaneus miscarriages and
a healthy son, FISH using Multi-T probe device disclosed a 9q subtelomere
duplication as an insertion onto chromosome 7p close to the
apparently normal 7p subtelomeric region. The same rearrangement
was also present in her son, in her brother and her mother who was
reported as having experienced repeated abortions. FISH probes from
other commercial sources were not able to confirm duplication of 9q
subtelomeric region onto 7p. Fiber-FISH experiments revealed that the
different commercially available 9q subtelomeric probes actually span
different 9q regions being only the most distal one able to display the
9q duplication.
Further studies on large series of patients will allow to establish repeated
miscarriages as an indication for subtelomeric analysis. The
finding that various FISH probes reported as specific for the same subtelomeric
region map at different chromosomal sites could be relevant
for subtelomere analysis.
P0397. Case report: Patient with ring chromosome 4
J. Huber1 , E. S. Ramos1 , D. G. Melo2 , L. R. Martelli1 ;
1 2 University of São Paulo, Ribeirao Preto, Brazil, Federal University of São
Carlos, São Carlos, Brazil.
Ring chromosome formations are rare structural chromosome aberration.
Most of them are sporadic cases. Patients with ring chromosome
4 are rarely observed. They associate concomitant loss of the telomeric
4p and 4q regions and lead to variable clinical manifestations depending
on the size of the deleted chromosomal material. The authors report
a 2 years old male patient with a near normal psychomotor development,
some minor dysmorphism and with cytogenetic analysis from
lymphocytes showing a mosaic karyotype 46,XY,r(4)[86]/46,XY[14].
Fluorescence in situ hybridization (FISH) study was also performed.
We compare the phenotypic appearance of our patient with the previously
reported cases of ring chromosome 4 in the medical literature.
P0398. Clinical features of a case with ring chromosome 18
M. Zamanian 1 , F. Mahjoubi 1,2 , S. Soleimani 1 , M. Rahnama 1 , F. Mortezapour 1 , F.
Razazian 1 , F. Manouchehri 1 , F. Nasiri 1 ;
1 IBTO, Tehran, Islamic Republic of Iran, 2 NRCGEB, Tehran, Indonesia.
Rings of chromosome 18[r(18)] are frequent among ring chromosomes:
depending on the size of the deleted regions in 18p and 18q,
the clinical symptoms of r(18) correspond more or less to the typical
signs of the 18p and 18q deletion syndromes. Ring chromosome 18
[r(18)] syndrome is characterized by mild to moderate learning disability,
behavioural disorders, and various dysmorphic features.
Here we report an additional case of a 14 months girl with r (18). The
girl was born at term after an uncomplicated pregnanacy and delivery.
Birth weight was about 1.5 kg, length 48cm, and head circumference
36cm. The girls presented hypertelorism, hypotonia, epicanthal folds,
abnormal fingers, low set ears, and abnormally growth teeth. Echocardiography
indicated dilation of the aorta.
Karyotyping after lymphocyte culture at the age of 14 months revealed
46,XX,r(18)(q21.2qter). The parent had normal karyotype.
The clinical feature of our case is mostly compatible with the other reported
cases of r(18) except the presence of abnormal teeth and heart
problem. This report further contribute to to the clinical of the r(18).