2008 Barcelona - European Society of Human Genetics

Prenental diagnostics
Here we describe two affected foetuses .
During the first pregnancy, an increased nuchal translucency was identified
at 12 WG. Chromososomes on Chorionic Villus Sample (CVS)
were normal 46, XX . Secondarily, heart abnormalities and a bilateral
cleft lip and palate were noted .
This multiple congenital anomalies syndrome led to termination of
pregnancy at 20 WG . Pathology examination revealed severe hypertelorism,
microtia, bilateral cleft lip and palate .
HMC syndrome was suspected and since it is an autosomal recessive
inherited defect, the genetic counselling was cautious . We recommended
close detailed ultrasound follow-up for further pregnancies .
During the second pregnancy, a recurrence was observed . Indeed,
the foetal ultrasound showed at 12 WG an increased nuchal translucency
and a right cleft lip . Chromosomes on CVS were normal 46,
XY . Pathology processed after the termination of pregnancy at 16 WG
revealed hypertelorism, small ears and a right cleft of the upper lip .
The parents are non consanguineous . Their karyotypes are normal . A
CGH-array study is pending on the first foetus. So far no responsible
gene is known for the HMC syndrome and the hypothesis of chromosomic
abnormality remains plausible .
P03.37
First successful prenatal diagnosis of mDc1A form in tunisia
revealed intrafamilial phenotypic variability in two siblings
sharing the same mutation in LAMA gene
O. Siala 1 , F. Kammoun 2 , N. Louhichi 1 , I. Hadj Salem 1 , M. Gribaa 3 , H. Eghezal 4 ,
A. Saad 4 , C. Triki 2 , F. Fakhfakh 1 ;
1 Laboratory of Human Molecular Genetics, Sfax, Tunisia, 2 Service de Neurologie,
C H U Habib Bourguiba, Sfax, Tunisia, 3 Laboratory of Human Molecular
Genetics, Sousse, Tunisia, 4 Department of Cytogenetics and Reproductive
Biology, Farhat Hached University Teaching Hospital, Sousse, Tunisia, Sfax,
Tunisia.
MDC1A is a severe congenital muscular dystrophy caused by mutations
in LAMA2 gene encoding the laminin α2 chain. Prenatal diagnosis
represents prevention for many couples given the overwhelming
prospect of having another child with this incurable condition . We
report the first prenatal diagnosis of MDC1A form in Tunisia and in
Africa in a family with previously affected child and identified mutation
in LAMA2 gene. Amniotic fluid was sampled by amniocentesis under
ultrasound guidance . Molecular analyses were performed on cultured
amniotic fluid cells after exclusion of maternal cell contamination by
QFPCR . Postnatal clinical examination was also performed by cerebral
MRI and by immunostaining on muscle biopsies using two monoclonal
antibodies directed against the laminin α2. After exclusion of
maternal cell contamination, mutation screening on fetal DNA showed
that he was homozygous for the c .8007delT frameshift mutation, and
the couple was counselled that the foetus would be affected . The presence
of the mutation was confirmed on total DNA extracted from blood
leukocytes of the newborn . Surprisingly, postnatal clinical examination
showed that the younger patient who was diagnosed as affected developed
widely milder phenotype of MDC1A form than his severely
affected brother; and immunfluorescence showed complete deficiency
of the laminin α2 in both patients. These findings suggest that other
genetic/or epigenetic factors including modifier gene can control the
course of the disease . Moreover, the intrafamilial phenotypic variability
in siblings with the same molecular defect complicates the diagnoses
because presymptomatic LAMA2 mutation carriers can develop a different
phenotype than pervious diagnosed porosities .
P03.38
indications for cordocentesis and correlation with chromosomal
aberrations
B. O. Petrovic1 , A. Ljubic1 , J. Joksimovic2 ;
1 2 Institute for gynecology and obstetrics, Belgrade, Serbia, Medicines and medical
devices agency of Serbia, Belgrade, Serbia.
Over a 7 years period we performed 734 cytogenetic analysis of foetal
blood taken by cordocentesis . Cordocenteses was performed because
of late gestation . Indications for cordocentesis were advanced
maternal age, increesed risk determined by biochemical screening or
sonographically detected foetal abnormalities. Indications and findings
are given in table 1 .
Table 1 .
Total Aberrant %
Biochemical Screening Risk 181 2 1,1%
Advanced Maternal Age 249 18 7,2%
Polyhydramnion 79 10 12,7%
Olgohydramnion 50 2 4%
IUGR 111 4 3,6%
CNS Anomaly 48 3 6,3%
Foetal Hart Defect 16 4 25%
Total 734 43 5,85%
In nearly 6% of analysed samples we found aberrant karyotypes. The most common
finding was autosomal aneuploidy. Trisomy 21 correlated with advanced maternal
age, polyhydramnion and foetal hart defects, while trisomy 18 was predominately
found in foetuses with CNS abnormalities. Structural chromosomal abnormalities were
detected only in 5 cases (0,7%), and had diferent phenotypic expression.
P03.39
case Report: submicroscopic duplication of D18s535 ina fetus
with normal karyotype
G. Dimisianos, R. Neroutsou, E. Manolakos, P. Tsoplou, A. Metaxotou;
BIOIATRIKI SA, Athens, Greece.
QF PCR (Quantitative Fluorescent PCR) was introduced only a few
years ago to speed up prenatal diagnosis and act as an adjuvant to
standard karyotype analysis . QF PCR utilizes length polymorphisms
of Short Tandem Repeats (STR) on selected chromosomes that are
amplified and then detected by automatic genetic analysers. STRs are
found in abundance in the human genome and their usefulness as potential
forensic markers for human identification purposes with the help
of PCR has been noted almost 20 years ago . Many STRs have been
utilized in the field of prenatal diagnosis leading to the development of
QF PCR (Quantitative Fluorescent PCR) with the concurrent advance
of technology in genetic analyzers . Here we report a case of a submicroscopic
duplication of STR D18S535 in an amniotic fluid sample
screened routinely for aneuploidies . This partial trisomy involving the
chromosome 18 was diagnosed by detecting this pattern only in one
out of three markers used for chromosome 18 . The rest of the STRs of
chromosome 18 tested were normal . After screening the parents it was
found that the extra allele had been inherited by the father so the pregnancy
continued normally . Conventional cytogenetic analysis that was
performed on this amniotic fluid had a normal karyotype. There have
been reports of other such duplications in the literature and stringent
screening is required to avoid false positive results when screening for
aneuploidies .
P03.40
Prenatally detected trisomy of chromosome 21
I. I. Kavecan, J. Jovanovic Privrodski, M. Kolarski, A. Krstic, L. Gacina, V. Cihi,
J. Rudez, T. Tarasenko;
Institute for Children and Youth Health Care Vojvodina, Novi Sad, Serbia.
We present incidence of prenatally detected trisomy of chromosome
21 during last seven years (2000-2007) in Medical Genetic Centre in
Novi Sad, Vojvodina northern part of Serbia with 2 .000 .000 inhabitans
.
Suspicion for trisomy 21 and indications for invasive prenatal diagnosis
was made by Clinical Genetics according maternal age (35 and more),
paternal age (42 and more), family pedigree, biochemical screening,
expert ultrasound result such as enlarged nuchal translucency, absent
nasal bone, echogenic bowels, short femur, and other .
During last seven years we detected 99 trisomy of chromosome 21
(full trisomy 91 cases, mosaicism 5 cases, translocations 3 cases),
that is 38 .98% of all prenatal detected chromosomal anomalies (N=
99/254; 38 .98%) .
P03.41
screening for different chromosome 18 methylation patterns
between placenta and whole blood
L. Rueda 1,2 , E. Ordoñez 1,2 , P. Cañadas 1 , W. Puszyk 3 , F. Crea 3 , R. Old 3 , C. Fuster
2 , V. Cirigliano 1,2 ;
1 General Lab, Barcelona, Spain, 2 Departament de Biologia Cel•lular, Universitat
Autònoma de Barcelona, Barcelona, Spain, 3 University of Warwick, Warwick,
United Kingdom.
Since its discovery in 1997, the presence of free fetal DNA in maternal
plasma provided new approaches for non invasive prenatal diagnoses .