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

Genetic analysis, linkage, and association
(69.2%) than in the CON group (36.1%) (odds ratio of 4.0; 95% CI
2.0-7.9; pT transition at nucleotide 414 of exon 66 of COL5A1 (rs12722).
Gender, age and the COL5A1 BstUI RFLP genotype contributed significantly
to the optimal SLR model. The factors contributing significantly
to SR were weight, age and the COL5A1 BstUI RFLP genotype. This
data suggests that the COL5A1 gene may be associated with lower
limb flexibility.
P0939. Analysis of a functional catechol-O-methyltransferase
gene polymorphism in healthy females: association with
aggressive behavior
M. Kulikova, N. Maluchenko, A. Tonevitsky;
Moscow State University, Moscow, Russian Federation.
Several lines of research have reported that functional polymorphism
in the catechol-O-methyltransferase (COMT) gene that is responsible
for substantial variability in COMT enzymatic activity is associated with
aggression and impulsivity. The most of recent researches have been
conducted on males therefore we suggest that it is important to investigate
an association of aggression with COMT genotypes in females.
A common low-activity variant of the enzyme contains a Met residue
at amino acid 158 of COMT whereas the common high activity variant
has a Val at this site. Considering the role of COMT in dopamine metabolism
and the involvement of dopaminergic pathways in the formation
of aggression, we screened athletes (78 females) and non-trained
control group (83 females) to determine whether a behavioral association
with the COMT polymorphism exists or not. Case-control analyses
suggested a strong association between the ValVal genotype in both
groups and high aggressive and dangerous behavior (P < 0.04). Also
we have found that allele distribution is different in the groups and it
could be the evidence of genetic propensity in sports.
P0940. Congenital cataract - a national wide study in Denmark
L. Hansen 1,2 , H. Eiberg 1 , K. Kjaer 1,2 , T. Rosenberg 3 ;
1 Copenhagen University, Copenhagen, Denmark, 2 The Wilhelm Johannsen
Centre for Functional Genome Research, Copenhagen, Denmark, 3 , Kennedy
Institute-National Eye Clinic, Copenhagen, Denmark.
Inherited congenital cataract leads in most cases to loss of vision if it
not treated. Congenital cataract is present at or develops shortly after
birth. Mutations in more than 20 human genes have now been associated
with congenital cataract and mainly in combination with autosomal
dominant inheritance.
A study of 30 Danish families with inherited congenital cataract has
been initiated in order to identify the disease causing mutations. Mutations
were found in 16 families and analyses of the remaining fami-
2 2
lies are in progress. Mutations have been identified in seven different
genes revealing both known and novel mutations.
The methods include genome wide linkage analyses, locus specific
STS marker analyses of cataract loci or direct DNA sequencing of
cataract genes. The analysis comprises all known congenital cataractassociated
genes and the analyses may be applied for medical genetic
counseling in the future.
The results from the first 16 families demonstrated mutations in the alpha-,
beta- and gamma- crystallin gene families, the alpha gap junction
gene family, the heat shock factor genes and in regulatory genes.
Several of the families represent distinct cataract phenotypes as the
ant-egg-cataract (1) and the combination of microcornea and cataract.
The results, the geno-/phenotypic relations and the structural and functional
consequences of the mutations will be presented at the meeting.
1) Hansen L, Yao W, Eiberg H, Funding M, Riise R, Kjaer KW, Hejtmancik
JF, Rosenberg T. The congenital “ant-egg” cataract phenotype
is caused by a missense mutation in connexin46. Mol Vis. 2006;
12:1033-1039.
P0941. Linkage screening in a large Iranian family with
congenital motor nystagmus (CMN)
A. Kian Mehr 1 , Y. Shafeghati 1 , H. R. Khorram Khorshid 1 , H. Ebrahimi 1 , Y. Heshmati
1 , M. Karimlou 2 ;
1 Genetic Research Center, University of Social Welfare and Rehabilitation Sciences,
Tehran, Islamic Republic of Iran, 2 Biostatistics department, University of
Social Welfare and Rehabilitation Sciences, Tehran, Islamic Republic of Iran.
Idiopathic congenital motor nystagmus (CMN) is a genetic disorder
characterized by bilateral ocular movements that start within early
months of life. To date different typs of inheritance patterns have been
reported for CMN, but no causative gene has been determined for
CMN so far. This Iranian pedigree shows a typical X-linked dominant
pattern with reduced penetrance (about30%) among obligate carrier
females. There is no male to male transmission. Investigations have
been done so far indicated five out of six families with X-linked CMN to
be linked to a nearly distinct area in long arm of chromosome X . We
designed linkage screening for some microsatellite markers previously
confirmed for linkage on chromosome X. Linkage study was performed
on Xp by DXS993 ruled out linkage to this locus. The second marker
on Xq,DXS1047 , was not informative in our Iranian population. Our
study on other markers on Xq is under way.
P0942. Insertion/deletion polymorphism of Angiotensin
Converting Enzyme (ACE) gene in children with connective
tissue dysplasia.
I. A. Kostik 1 , M. L. Chukhlovina 2 , V. I. Larionova 2 , T. I. Kadurina 1 ;
1 Medical Academy Postgradute Studies, Saint-Petersburg, Russian Federation,
2 State Pediatric Medical Academy, Saint-Petersburg, Russian Federation.
Connective tissue dysplasia (CTD) is a group of geterogenous diseases
with hereditary and inborn collagen synthesis disturbance. These
patients have different neurological complaints, such as, headache,
weakness, fatigue, dizziness, syncope, lypothymia, associated with
cerebral hemodynamic disturbance. Previous studies have suggested
an influence of ACE gene alleles on cerebrovascular disorders (CVD)
in adults and children.
The aim of our study was to investigate the relationship between ACE
gene polymorphism and cerebrovascular disorders in these children.
One hundred and three CTD children (36 girls, 68 boys) were included
in our study. The mean age of patients was 12.97 ±3.93 years, 61,0%
had CVD. Total genomic DNA was extracted by a standard method
and ACE genotypes were determined using polymerase chain reaction
(PCR) followed by analysis of PCR products by agarose gel electrophoresis
in 41 children.
We have revealed the next genotypes and alleles distribution in these
children: II-31,7%, ID-39,0%, DD-29,3%; I-51,2% and D-48,8%. We
have no significant differences in ACE genotypes and alleles distribution
between boys and girls. The incidence of homozygous deletion
(DD) genotype in children with CVD was 37,5% compared to 25,0%
in children without CVD. Children with II genotype had CVD only in
16,7% cases, but children with ID genotype had CVD in 42,9% cases
and children, carriers of DD genotype had CVD in 50,0% cases.
Conclusion: the role of ACE gene insertion/deletion polymorphism in
cerebrovascular disorders in children with connective tissue dysplasia
still needs to be determined.