2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
deletions in a large proportion of known MRX genes . Because of its
low cost and sensitivity it is suitable for routine diagnosis of X-linked
mental retardation .
P06.316
the chromosome abnormalities, Y-chromosome microdeletions
and cFtR gene mutations testing of infertility man from Western
Ukraine
M. Tyrkus, N. Huleyuk, O. Bilevych, D. Zastavna, H. Makukh;
State institution “Institute of Hereditary Pathology of Academy of Medical Science
of Ukraine”, Lviv, Ukraine.
The most widespread genetic factors causing male infertility include
different quantitative and structural chromosome abnormalities, Ychromosome
microdeletions and CFTR gene mutations .
DNA and cultivated leukocytes from peripheral blood of 150 males with
spermatogenesis failure were analyzed .
Cytogenetic analysis revealed Klinefelter’s syndrome - 47, XXY (7 persons),
de la Chapelle syndrome - 46, XX (3), disomy of Y-chromosome
- 47, XYY (1) . Totally quantitative and structural chromosome abnormalities
were found in 13 males (9%) .
Any changes in the structure of Y-chromosome hadn’t been found in
males with Klinefelter’s syndrome . In patients with 46, XX karyotype
whole sequence of AZFa, AZFb and AZFc is absent . Among 3 patients
with de la Chapelle syndrome SRY gene had been detected in 2 persons
.
We detected various cases of AZF gene subregions deletions: AZFa
(1 patient), AZFb (1), AZFb+c (1), AZFc (6) . Whole absence of PCR -
product of AZFa, AZFb and AZFc and SRY gene was detected in male
with azoospermia and normal karyotype that requires next sequencing
analyses . Thus, in 7% of examined infertile males with normal karyotype
Y-chromosome microdeletions were found . In regard to the group
of examined infertile males the percentage of Y-chromosome microdeletions
reached approximately 10% .
The molecular-genetic analysis of CFTR gene mutations and
IVS8polyT polymorphic locus revealed F508del mutation in 4 persons,
5T polymorphic allele - in 12 males with spermatogenesis failure .
The studies point on high effectiveness of the complex of cyto- and
molecular-genetic researches in males with impaired fertility and state
their necessity in diagnose .
P06.317
ZNF 0 in psoriasis
R. Y. Birnbaum 1 , A. M. Bowcock 2 , I. Cohen 1 , S. Sivan 1 , R. Ofir 1 , O. S. Birk 1 ;
1 National Institute for Biotechnology in the Negev, Beer-Sheva, Israel, 2 Department
of Genetics, Washington University School of Medicine, Saint Louis, MO,
United States.
We have previously shown that a dominant mutation in ZNF750 underlies
seborrhea-like dermatosis with psoriasiform elements . To assess
the contribution of ZNF750 to the pathogenesis of bone fide psoriasis,
we screened 250 psoriasis patients from the U .S . for mutations in the
3 exons of ZNF750, the intron-exon boundaries and 1000bp upstream
sequences . While no mutations were found in the coding region, a heterozygous
ZNF750 5’ UTR variant (+46 C>T) was seen in 3 unrelated
psoriasis patients . This change was not found in 300 healthy control
samples . Our data suggest that the ZNF750 5’ UTR variant (+46 C>T)
might be associated with psoriasis
P06.318
β 2 -adrenergic receptor (ADRB2) polymorphisms in the childhood
asthma
E. A. Isupova, G. A. Novik, V. I. Larionova;
Saint-Petersburg State Pediatric Medical Academy, Saint-Petersburg, Russian
Federation.
Gene polymorphisms of ADRB2 are candidate gene of genetic predisposition
to bronchial asthma (BA) and allergic diseases . From data of
literature the genetic variants of cellular receptors possibly influence
on efficiency of action of antiasthmatic drugs.
The aims of our study was to investigate genotypes and alleles frequency
of two common polymorphisms of ADRB2 gene (Arg16Gly and
Gln27Glu ) in boys and girls with different severity BA .
Patients and methods: 160 Caucasians children, 129 boys (81%) and
31 girls (19%) with the set diagnosis of bronchial asthma of different
severity were included . Mild astma was diagnosed in 10 children (6%),
75 children (47%) had moderate asthma and 75 children (47%) had
severe asthma. Two common ADRB2 polymorphisms 16 (Q→E) and
27 (G→R) were detected by PCR method with the subsequent restriction
assay .
Results: we have revealed association between distribution of haplotypes
ADRB2 and severity of BA . Patients with the severe asthma had
sighnificantly more frequent haplotype EE/GG than patients with moderate
asthma (p=0,024) in which more frequent where was haplotype
QQ/GR . In group of boys we detected analogical changes (p=0,017),
but there were no differences in girls .
P06.319
No significant role of the FXII 46C→T mutation in Spanish and
tunisian cardiovascular patients
G. Athanasiadis 1 , E. Esteban 1 , M. Gayà-Vidal 1 , M. Resano 1 , R. Carreras Torres
1 , H. Chaabani 2 , P. Moral 1 ;
1 Unitat d’Antropologia, Dpt. de Biologia Animal, Facultat de Biologia, Universitat
de Barcelona, Barcelona, Spain, 2 Faculté de Pharmacie de Monastir, Monastir,
Tunisia.
Background.- The 46C→T polymorphism in the Coagulation Factor XII
gene consists of a cytosine to thymidine transition at the position 46
from the transcription initiation point in exon 1 of the 5´-untranslated
region . Previous case-control studies have indicated an association
between this polymorphism and variation in plasma levels of FXII . The
46C→T seems to affect the translation efficiency, leading to reduced
plasma levels of the protein . It has been inferred that this mutation accounts
for 40% of the variance in FXII activity levels in a Spanish Mediterranean
population . As other case-control studies in the same region
indicate, genotype T/T is an independent risk factor for venous thrombosis,
ischemic stroke and acute coronary artery disease (CAD) .
Aim.- In this study, we try to confirm the importance of the 46C→T
polymorphism in two patient samples from Spain and Tunisia .
Methods.- We have implemented two different approaches: a Transmission
Disequilibrium Test (TDT) based on 101 families (N=302) from
Spain (Barcelona) with one offspring with CAD; and a classical casecontrol
study based on 76 patients with CAD complicated by myocardial
infarction and on 118 healthy individuals from North and Centre-
South Tunisia. All subjects were genotyped for the 46C→T polymorphism
with Real-Time PCR using a TaqMan® SNP Genotyping Assay
(Applied Biosystems) and the appropriate software was implemented
for the data analyses .
Results.- No statistically important association was detected in any of
the two samples (TDT: p=0 .16, statistical power = 99%; case-control
study: p=0 .65) .
Conclusion.- The results suggest that 46C→T is not a risk factor for
CAD in any of the two analysed samples . So far as we know, the TDT
analysis for this mutation is the first one carried out in a Spanish population
and suggests that 46C→T might not be the only functional site
that would explain the susceptibility to thrombotic disease .
P06.320
Bsmi, Apai and taqi Polymorphisms of Vitamin D receptor gene
in turkish nephrolithiasis patients
N. Ersoy, K. Incekara, O. Kose, O. Cakir;
Halic University, Department of Molecular Biology and Genetics, Istanbul, Turkey.
Nephrolithiasis is a multi-factorial disease influenced by genetic, hormonal
and environmental effects . Calcium oxalate (CaOx) is the most
common constituent of kidney stones . Vitamin D receptor (VDR) involves
in controlling the effects of 1,25dihydroxyvitaminD 3 . The 3’UTR
region of the VDR gene includes a cluster of polymorphisms: BsmI,
ApaI and TaqI . These polymorphisms have been studied in patients
with urolithiasis, but yielded inconclusive results . Since the contribution
of alleles may appear to be different in different ethnic populations,
the relationship of the individual and combined polymorphisms should
be studied for each population . In this study, we investigated the association
of BsmI, ApaI and TaqI polymorphisms in 98 Turkish CaOx
stone patients and 70 controls . 52% of the patients reported a family
history of stones . The polymorphic sites were amplied with PCR, subjected
to restriction enzyme digestion and analyzed on agarose gels .
Associations between the disease and genotypes were assessed by
calculating odds ratios and 95% confidence intervals. VDR genotype
distribution was compared with that of controls using the chi-square