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

Molecular and biochemical basis of disease
sorineural hearing loss was co-existed with goiter. Further studies are
needed to confirm pathogenicity of some mtDNA variations associated
with deafness in patients from some regions of Russia.
P0810. Common polymorphism of A1298C in MTHFR gene
is associated with maternal meiosis I chromosome 21
nondisjunction in Down syndrome
S. Rezaee, A. Aleyasin;
National Institute for Genetic Engineering and Biotechnology, Tehran, Islamic
Republic of Iran.
Parental origin and stage of meiotic error of chromosome 21 nondisjunction
has been determined in 226 families with Down syndrome.
Their mothers hav e been genotyped for common polymorphisms in
the MTHFR (C677T and A1298C) and MTRR (A66G) genes to identify
any specific association of these previously described maternal
genetic risk factor to the etiology of chromosome 21 nondisjunction.
Five STR markers related to chromosome 21 (D21S11, D21S1414,
D21S1440, D21S1411, D21S1412) were used to determine the parental
origins and stage of meiotic error successfully for 226 cases.
In total, 140 cases showed a meiotic error in meiosis stage I, 58 in
meiosis maternal meiosis stage II, 20 in paternal meiosis I and 8 in
paternal meiosis II. All four groups of mother cases and a normal control
group consisted of 176 normal mothers with at least one healthy
child were tested for common polymorphisms of C677T, A1298C in
the MTHFR and C66G in the MTRR genes. Significant association
was detected between maternal meiosis I chromosome 21 nondisjunction
and the A1298C polymorphism of the MTHFR gene (P11.13). This study has showed for the first time the importance of
stage of meiotic nondisjunction in the study of maternal genetic risk
factor of Down syndrome. The significant association of stage I meiotic
nondisjunction and A1298C polymorphism of MTHFR gene in mother
of Down syndrome presents the relationship of acid folic metabolism in
the etiology of Down syndrome in Iranian cases.
P0811. Is the MTHFR C677T gene polymorphism a modifier
factor in SMA?
P. Apostol1 , D. Cimponeriu1 , M. Stavarachi1 , I. Radu1 , L. Dan1 , L. Cherry1 , M.
Toma1 , N. Butoianu2 , C. Burloiu2 , S. Magureanu2 , L. Gavrila1 ;
1 2 Institute of Genetics, Bucharest, Romania, Alexandru Obregia Hospital, Bucharest,
Romania.
The methylation process is essential for the regulation of genes expression
controlling the development and function of the neurons. The
formation of SMN complex, responsible for motoneurons survive, is dependent
by the symmetric dimethylation of some component proteins.
We speculated that this interaction could be affected by the MTHFR
gene although any data regarding this association are not available.
The MTHFR C677T polymorphism is strongly associated with the reduction
of MTHFR activity. Based on this observation, we analyze a
possible association of this polymorphism with the SMA severity in the
Romanian patients.
Our study was carried out on 63 SMA clinically diagnosed patients,
classified by ISMAC criteria, 60 parents and 100 controls. The blood
samples were obtained from Bucharest pediatric hospital. Informed
oral consent was obtained from all subjects. The MTHFR C677T gene
polymorphism was analyzed by PCR-RFLP method.
The highest frequency of TT genotype was observed in the SMA III
group (21,05%) compared with SMA II (17,6%) and I (14,8%), and with
parents (13,3%) and control (7%) groups. This genotype may increases
the risk for disease in SMA type I (OR = 2,31) and II (OR =2,84),
while in SMA type III, only the presence of one T allele was associated
with the disease.
We can not exclude the contribution of mutated allele to the SMA phenotypes
because our lots are not very large.
MTHFR677CC MTHFR677CT MTHFR677TT
SMA 19 33 11
Parents 22 30 8
Control 48 45 7
21
P0812. A66G polymorphism of methionine synthase reductase
(MTRR) gene is associated with spontaneous abortions
O. N. Bespalova 1 , T. E. Ivaschenko 1 , N. I. Matveeva 1 , I. Y. Vasileva 2 , V. S.
Baranov 1 ;
1 Institute of Obstetrics & Gynecology, St. Petersburg, Russian Federation, 2 Diagnostic
medical genetical Center, St. Petersburg, Russian Federation.
Spontaneous abortion (SA) is a frequent health problem of women of
the reproductive age. A number of causes including uterine anomalies,
maternal\paternal balanced translocations, luteal phase defect,
hyperhomocysteinaemia have been attributed to the origin of SA.
MTRR is an enzyme essential for normal folate metabolism. A common
polymorphism in this gene was recently found to be associated
with increased risk of neural tube defects. It also might contribute to
increased risk for SA.
The 66A\G polymorphism of the MTRR gene was studied by PCR-
RFLP analysis in 108 women with one and more normal pregnancies
and no SA in anamnesis (control group I) , in 78 nonpregnant women
with a history of at least one SA (II group), in 75 patients with two recurrent
SA (III group) and in 67 patients with numerous ( >- 3) recurrent
SA(IV group).
The distribution of genotype frequencies for MTRR gene was significantly
different (p