2008 Barcelona - European Society of Human Genetics

Prenental diagnostics
P03.60
the results of perinatal testing from istanbul memorial Hospital
C. Aslan1 , G. Ozgon1 , O. Oner1 , B. Onal1 , F. Fiorentino1 , C. Yilanlioglu2 , S.
Kahraman2 ;
1 2 Genoma Turkey, istanbul, Turkey, Memorial hospital, istanbul, Turkey.
Introduction
The aim of this study is the retrospective data collection of patients
(especially PGD patients) between 2000-2007 for amniocentesis and
for cvs between 2003-2007 to understand that the PGD might be a
reasonable option for translocation carriers, advanced maternal age
(ama), single gene disorder (sgd) carriers, patological USG findings,
recurrent implantation failure (rif), recurrent pregnancy lost (rpl), bad
obstetric history .
Mat- method: Cell cultures were used for amniotic fluid specimens and
tissue culture for coryon villi sampling (CVS) . Culture developments
were observed and underwent harvesting steps in the optimum timing
(after 10-12 days) . Slides were stained with giemsa staining techniques
(GTG) and 30 cells were counted .
Between years 2000-2007, amniocentesis were performed to 615 patients
and 82 CVS between 2003-2007 in our center . The indications
and chromosome analysis results are in the table .1 below .
Results:
Table1 Results of amniosentesis
FISH (n=55)
PGT (n=91)
Single gene
disorder(n=36)
Normal or balanced
(n=54)
Abnormal(n=1)
mosaic 47,XXY
Normal or balanced
Normal (n=36) -
Normal (n=141) - -
Trisomy 18
IVF(n=146)
Abnormal (n=5)
Patologic USG(n=3)
Mosaic X
46,--,t(1;2)(p36 .1;q12),del(2)(q1
2q13)
Maternal age (n=1) Trisomy 18
Translocation (n=1) 46,--,dic(8),t(8;18)(q13;q11 .1)
Normal(n=361) - -
Trisomy21(n=4)
Tryploidy
Patologic USG(n=7) 45,X
46,--,t(4;6),t(5;6),t(11;18),der(9)
add(9)
Spontaneous
(n=378)
Abnormal triple test
(n=2)
Abnormal (n=17)
Translocation (n=4)
Trisomy21(n=2)
46,--,t(2;7)
46,--,;recp t(13;16)
46,--, t(10;13)
inv(10)
Male factor (n=1) Mosaic X
Trisomy 18
Maternal age (n=3) Tryploidy
Mosaic XXY
Table.2 Results of CVS
Indications Chromosome Analysis Results
AMA (n=8) Normal (n=8)
Abnormal First Trimester Normal (n=29)
Test(n=30)
Trisomy 21
Normal (n=10)
Trisomy 18
Trisomy 21
Patological USG Findings (n=16) Mosaic X
45,X
46,--,t(3;11),t(5;14)
47,--,der(15)t(4;15)
Bad Obstetric History (n=5) Normal (n=5)
Male Factor (n=2)
Normal (n=1)
46,--,inv(12)
Abnormal Triple Test (n=2) Normal (n=2)
Single gene Normal
+HLA(n=9)
(n=9)
PGD Cases (n=12)
PGD FISH(n=3)
Normal
(n=2)
46,--
,t(10;12)
Discussion: In this study, we present that performing amniocentesis and cvs cultures
and karyotype analysis approve that PGD is a reliable option for the patients with
several indications to have a non-affected offspring.
P03.61
Pathological cytogenetical findings in fetal prenatal diagnosis
J. Jovanovic Privrodski, I. Kavecan, A. Krstic, L. Gacina, M. Kolarski, V. Cihi,
J. Rudez, T. Tarasenko;
Institute for Children and Youth Health Care Vojvodina, Novi Sad, Serbia.
In Medical Genetic Centre in Novi Sad (Institute for Children and Youth
Health Care Vojvodina), prenatal genetic screening of fetal abnormalities
is performed using detailed analisys of pedigree, maternal and
paternal age, biochemical screening (pregnancy associated plasma
protein -PAPP-A, free beta-subunit of human chorionic gonadotropin
-free beta hCG in 11-14th weeks of gestation; alpha-fetoprotein -AFP,
unconjugated estriol -uE3, PAPP-A, in 16-18th weeks of gestation) and
expert ultrasound . If married couple have risk for fetal chromosomal
abnormalities, Clinical genetics indicate invasive prenatal diagnosis .
During last five years (2003-2007.) in Medical Genetics Centre in Novi
Sad were made 19019 Genetic consultations, and 11488 invasive prenatal
procedures (9938 amniocentesis, 1550 cordocentesis) . We found
169 pathological findings (1.47%), from amniocenthesis (N=145/9938;
1 .46%) and from cordocenthesis (N=24/1550; 1 .54%) . The most frequent
chromosomal anomalies was Down syndrome (42 .01%), Edwards
syndrome (9 .46%), Patau syndrome (5 .32%), Turner syndrome
(6 .51%), Klinefelter syndrome (9 .46%), and other chromosomal anomalies
(27 .24%) .
P03.62
Karyotyping vs MLPA in spontaneous (late) pregnancy losses.
T. Dijkhuizen, H. H. Faber, G. Drok, K. B. J. Gerssen-Schoorl, B. Sikkema-
Raddatz, K. Bouman;
Department of Genetics, Groningen, The Netherlands.
Early spontaneous abortions (less than 16 weeks of pregnancy) have
a variety of chromosome aberrations, most of them aneuploidies of
whole chromosomes . Chromosome abnormalities occur to a lesser
extent in second and third trimester pregnancy losses . Chromosome
analysis provides valuable information about the possible cause of fetal
death and the recurrence risk . Yet it is hampered by a high rate
of culture failure. Multiplex Ligation dependent Probe Amplification
(MLPA) overcomes the problem of culture failure if DNA is extracted
directly out of the fetal tissue before culture . Using a subtelomere dedicated
test, it can provide information on the ploidy status of all chromosome
(arm)s .
In the present study we compared routine chromosome with MLPA
analysis in a series of more than hundred fetal tissue samples of spontaneous
(late) second and third trimester pregnancy losses . Routine
chromosome analysis succeeded in 20% of cases, of which 8% had an
abnormal chromosome complement . For MLPA, two different subtelomere
specific tests (P036 and P070) were used to examine all chromosomes
for ploidy status . We obtained interpretable results in 83% of
cases . Abnormal ratio spreads were observed in 6% of them . Detailed
data will be presented on the poster .
In conclusion, MLPA increases the success rate for chromosome
analysis dramatically by overcoming the problem of culture failure . Although
it is suggested that culture failure could be caused by the fact
that the fetus has a chromosome abnormality, the percentage of genetically
abnormal tissue samples remains similar for both techniques,
MLPA and karyotyping .
P03.63
Prenatal diagnosis of mosaicism for different structural
unbalanced cell lines involving chromosome 18
A. Soler1,2 , J. Bruguera3 , I. Mademont4 , C. Morales1 , N. Clusellas1 , C. Badenas1,2
, A. Sánchez1,2 ;
1Servei de Bioquímica i Genètica Molecular. Hospital Clinic, Barcelona, Spain,
2 3 4 IDIBAPS, Barcelona, Spain, Fundació Clinic, Barcelona, Spain, CIBERER,
Barcelona, Spain.
Confined placental mosaicism is detected in 1-2% of pregnancies undergoing
first-trimester CVS. Structural mosaicism is a rare event, often
difficult to interpret. However, chromosome 18 appears to be most
frequently involved in these structural rearrangements, according to
published cases . We report a further case detected by prenatal diagnosis
. CVS was performed on a pregnant woman due to increased