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

Molecular and biochemical basis of disease
Stroke RSMU, Moscow, Russian Federation.
Consisting of a fragment of ACTH4-7 and C-terminal PGP tripeptide
neuroprotective polypeptide Semax is used for acute therapy of stroke.
To investigate Bdnf mRNA expression after treatment either with saline,
Semax or PGP the brains of male Wistar rats were analyzed at
three time points following permanent middle cerebral artery occlusion
(pMCAO): 3, 24 and 72 hours. The intraperitoneal injection of solutions
were done at 15 min, 1 h, 4 h after the occlusion and then after every
4 hours. The last injection was done at 56 h after operation. Real-time
reverse transcription and polimerase chain reaction has been used to
measure changes in Bdnf expression in the ipsilateral and contralateral
frontoparietal cortex and subcortex of rat brains. Gapdh was used
as the internal control.
In the lesioned cortex Bdnf mRNA expression was increased at 24
h post-MCAO and returned to control level after 72 h. Decreasing of
Bdnf mRNA expression in contralateral hemisphere 3 h after operation
is probably concerned with depolarization expansion and neuroplasticity.
Under Semax treatment in ischemic cortex such increasing of Bdnf
mRNA expression was detected at 3 h after operation and the level of
Bdnf mRNA was high at 24 and 72 h post-MCAO. Thus Semax supports
earlier increasing of Bdnf expression in the ischemic tissue and
helps to retain high level of Bdnf mRNA to the point of 72 h after occlusion.
C-terminal PGP tripeptide also increases Bdnf mRNA expression
3 h after ischemia but then Bdnf expression returned to control level.
P0871. A microdeletion on chromosome 1q21 is required but
not sufficient for development of thrombocytopenia-absent radii
(TAR) syndrome
E. Klopocki 1 , H. Schulze 2 , C. Ott 1 , F. Trotier 1 , G. Strauss 2 , H. Ropers 3 , R. Ullmann
3 , D. Horn 1 , S. Mundlos 1,3 ;
1 Charité Universitätsmedizin Berlin, Institute of Medical Genetics, Berlin, Germany,
2 Charité Universitätsmedizin Berlin, Klinik für Allgemeine Pädiatrie, Berlin,
Germany, 3 Max Planck Institute of Molecular Genetics, Berlin, Germany.
Thrombocytopenia-absent-radius (TAR) syndrome is a rare congenital
disorder with an incident of 1-2 in a million. TAR syndrome is characterized
by hypomegakaryocytic thrombocytopenia and bilateral radial
aplasia in the presence of both thumbs. Other frequent associations
are congenital heart disease and a high incidence of cow’s milk intolerance.
The molecular basis as well as the inheritance pattern for this
disorder is still ill-defined.
Here, we present evidence that a microdeletion of about 200 kb on
chromosome 1q21 encompassing about 11 annotated genes is essential
for developing TAR syndrome. We tested 32 individuals affected by
TAR syndrome from 30 unrelated families by submegabase microarraybased
comparative genomic hybridization (array-CGH), fluorescence
in situ-hybridization (FISH), or quantitative RT-PCR and detected the
microdeletion in all samples tested. The absence of this deletion in a
cohort of control individuals argues for a specific role of the microdeletion
in the pathogenesis of TAR syndrome. The microdeletion occurred
de novo in about 25% of pedigrees analyzed. Intriguingly, in the other
pedigrees inheritance of the deletion along the maternal as well as
the paternal line was observed. The deletion was also present in additional
unaffected family members spanning up to three generations.
Thus, it is obvious that the occurrence of the microdeletion is required
but not sufficient to cause TAR syndrome. We therefore conclude that
TAR-syndrome has to be considered a genetically complex disorder
rather than a monogenic disorder, suggesting the presence of a yet to
be identified modifier of TAR (mTAR).
P0872. The tau H2 haplotype contribute to susceptibility to
Parkinson disease in a Southern Italy population.
D. Civitelli, P. Tarantino, E. V. De Marco, F. Annesi, S. Carrideo, I. C. Cirò Candiano,
F. E. Rocca, G. Annesi;
National Research Council, Mangone, Italy.
There are many evidences that tau protein is involved in common neurodegenerative
pathways, and a number of association studies have
been conducted to clarify the role of the tau gene in neurodegenerative
diseases, including Parkinson’s disease (PD). A contribution of the H1
haplotype to PD susceptibility was suggested. Several polymorphisms
localized along the entire tau gene length are inherited in complete
linkage disequilibrium as 2 distinct extended haplotypes designated
H1 and H2, respectively. Here, we investigated the distribution of tau
haplotypes in a group of 262 sporadic PD patients from Southern Italy
22
compared with 197 healthy controls from the same area.
We reconstructed tau haplotypes genotyping 3 SNPs (BanII in exon
3, MspI in exon 9, AluI in exon 11) and a dinucleotide polymorphism
in intron 9. Of interest, we found a significant overrepresentation of
the H2 haplotype in PD patients ( OD 2.26 - 95% CI 1.64-3.18), suggesting
that the H2 haplotype is a risk factor for parkinsonism in our
sample. Southern Italy population appears different from most of other
Caucasian populations in which, on the contrary, the tau H1 haplotype
contribute to susceptibility to Parkinson’s disease.
P0873. Genetic screening for beta-thalassemia point mutations
using two-steps effective approach
L. Dan 1 , R. Talmaci 2,1 , L. Cherry 1 , D. Coriu 2,3 , M. Dogaru 3 , D. Cimponeriu 1 , A.
Pompilia 1 , D. Uşurelu 1 , L. Gavrilă 1 ;
1 Institute of Genetics, University of Bucharest, Bucharest, Romania, 2 University
of Medicine and Pharmacy Carol Davila, Bucharest, Romania, 3 Fundeni Clinical
Institute, Bucharest, Romania.
The occurrence of β-thalassemia in Romania is not so common. Taking
into account that thalassemia demography is in continuous changing,
a developing country should handle with its prevention. A first stage
to this objective is to characterize the molecular spectrum of β-globin
gene mutation in the respective population. One hundred and twenty
eight β-thalassemic chromosomes derived from ninety-four β-thalassemia
carrier and seventeen homozygous patients were investigated
for their β-globin mutations. Molecular screening approach was performed
in two steps: indirect scanning by DGGE followed by direct
PCR based methods - ARMS and PCR-RFLP. Applying this effective
approach, we were able to find a total of 12 mutations: IVS I-110 (G-A)-
43 chr., IVS I-6 (T-C)-21 chr., Cd 39 (C-T)-17 chr., IVS II-745 (C-G)-15
chr., IVS I-1 (G-A)-9 chr., Cd 6 (-A)-5 chr., -87 (C-G)-4 chr., Cd 8 (-AA)-
4 chr., Cd 5 (-CT)-3 chr., +22(G-A)-1 chr., Poly A (A-G)-1 chr., Cd 51
(-C)-1 chr. Besides these mutations, DGGE reveals four uncharacterized
mutations which remain to be sequenced. All the identified mutations,
less cd 51 (-C), are of Mediterranean origin which demonstrates
a gene flow from that area.
Funding from the European Commission for the “eInfrastructure for
Thalassaemia Research Network”, Coordination Action - Contract no
026539 - for which this study was partially funded is gratefully acknowledged.
P0874. Genetic Polymorphism in Deep Vein Thrombosis
H. Samli 1 , M. Emmiler 2 , C. U. Kocogullari 2 , A. Ozgoz 1 , M. Solak 1 , A. Cekirdekci
2 ;
1 Afyonkarahisar Kocatepe University, School of Medicine, Department of
Medical Biology, Afyonkarahisar, Turkey, 2 Afyonkarahisar Kocatepe University,
School of Medicine, Department of Cardiovascular Surgery, Afyonkarahisar,
Turkey.
A deep vein thrombosis (DVT) is a blood clot (thrombus) that develops
in a deep vein, usually in the lower leg. Factor V Leiden (FV Leiden)
(G1691A) mutation is one of the most important genetic factors causes
deep vein thrombosis. Another genetic thrombosis reason thought
to cause venous thrombosis tendency is Prothrombin Factor II (FII)
(G20210A) mutation. Some study reports on hyperhomosisteinemia
being a risk factor in DVT, made us think searching Methylenetetrahydrofolate
reductase (MTHFR) (C677T) gene polymorphism in this
patient group might be significant.
In our study 27 patients diagnosed to be DVT by Cardiovascular Surgery
experts and 31 healthy controls were investigated. In all cases
FV Leiden, FII and MTHFR gene polymorphism investigations were
performed by PCR-ELISA method.
Even though the result of genetic analysis performed for the frequency
of FV Leiden mutation and MTHFR gene polymorphism were detected
to be high in the patient group, it was not found to be statistically meaningful
(p>0,05). FII mutation was found to be significantly high in the
patient group (p