2009 Vienna - European Society of Human Genetics

Prenatal and perinatal genetics
24 h was equal to 3,1+3,09 % and they were detected only in the group
A, whereas after 48 h they were represented in both A (36,1+16,01 %)
and in M groups (10,5+4,20 %) (P 0.05) after 72 h incubation. No 3 rd generations cells
have been registered in both groups.
These results are consistent with some previous data which postulate
the duration of one complete cell cycle of CTB equal to approximately
36 h. However proliferative capacity in vivo of CTB cells from missed
abortion is reduced if compared to this one of progressive normal pregnancy.
P05.08
Relationship of circulating cell-free DNA levels to cell-free fetal
DNA levels, clinical characteristics and laboratory parameters in
preeclampsia
L. Lazar, B. Nagy, A. Molvarec, J. Rigó Jr.;
Semmelweis University, Budapest, Hungary.
Objective: Elevated amounts of circulating DNA in maternal plasma
have been detected in pregnancies complicated by preeclampsia. We
attempted to confirm this and simultaneously examined whether increased
circulating cell-free DNA levels are related to the clinical characteristics
and laboratory parameters of preeclamptic patients.
Study design: Circulating DNA was measured by real-time PCR in
plasma samples obtained from 67 women with preeclampsia and 70
normotensive pregnant women. Standard laboratory parameters and
C-reactive protein levels were determined by an autoanalyzer. Plasma
von Willebrand factor antigen levels were quantified by ELISA, while
plasma fibronectin concentration by nephelometry. Plasma malondialdehyde
levels were measured by the thiobarbituric acid-based colorimetric
assay.
Results: We confirmed that circulating total free and fetal DNA levels
are significantly elevated in pregnancies complicated by preeclampsia
(median: 11.395 vs. 32.460 and 0.001 vs. 0.086 pg/ul; P < .001). The
quantity of total plasma-free DNA did not correlate with most of the
laboratory parameters, except for serum aspartate aminotransferase
and alanine aminotransferase activities (correlation coefficient: 0.31;
P=0.012 and 0.46; P1y).
Study of the common mutations (PCR-ASO) and R426H (7% virilizing
forms in Spain) together with genomic DNA analysis for hybrid deletions/large
gene conversions to detect hemizygosity, semiquantitative
primer-extension for gene duplications carrying Q318X, microsatellite
typing to detect unknown homozygosity for rare alleles (complementary
sequencing).
Results: CYP21A2 segregated mutant alleles were detected in 13 patients:
3 compound heterozygous with I172N and null alleles (3 boys),
8 compound heterozygous with severe mutations and V281L, and 2
with two mild alleles. Sustained 17OHP levels confirmed CAH-21OHD
diagnosis of these “neonatal cryptic forms”. In 43, mutations were discarded
in both alleles and a carrier situation was detected in 4 (655G,
655G+Q318X,V281L, P453S). The normal variant Q318X in gene duplicated
alleles was detected in 2 additional samples. Absence of clinical
signs and normalization of 17OHP levels, in these remaining 45
cases, discarded the deficiency.
Conclusion: CYP21A2 genotyping proved useful as a second-tier
analysis. The deficiency was discarded in all the negative patients and
carriers. The genotypes in those CYP21A2 positive patients allowed
to discard a severe deficiency and were compatible with mild forms in
boys and girls (compound heterozygous with V281L) or virilizing forms
in boys (compound heterozygous with I172N).
P05.11
Prenatal diagnosis of Dandy Walker malformation: case report
D. F. Albu, C. C. Albu, M. Dumitrescu, E. Severin;
“Carol Davila” Univ Med Pharm, Bucharest, Romania.
A 35-year-old pregnant Caucasian female was referred at 20 weeks of
gestation for a routine prenatal ultrasound. Fetal monitoring was made
by ultrasound scans for fetal growth, congenital malformations, and
amniotic fluid volume. Information about family medical history was collected
too. Amniotic fluid samples were taken to perform prenatal cytogenetic
diagnosis because sometimes Dandy Walker malformation is
associated with chromosome aberrations. The woman was tested for
TORCH. Results: Ultrasound examination revealed a singleton pregnancy
with cerebellar malformation and associated anomalies: ventriculomegaly,
meningocele and hydrocephaly. Karyotype indicated a
normal cytogenetic female: 46, xx. No evidence of an infectious origin
was found. The pregnancy was terminated at 25 weeks of gestation
Autopsy findings confirmed the ultrasound diagnosis. Conclusions: a
sporadic case with Dandy Walker malformation was described; prenatal
ultrasound disclosed a positive result useful for pregnancy management
and counseling for abortion.
P05.12
importance of Routine Ultrasonography in Detecting Fetal
Karyotype Abnormalities in Low Risk Pregnancies
A. I. Narin 1 , Z. Yilmaz 1 , D. Eroglu 2 , F. Yanik 2 , F. I. Sahin 1 ;
1 Baskent University Faculty of Medicine Department of Medical Genetics, Ankara,
Turkey, 2 Baskent University Faculty of Medicine Department of Obstetrics