2009 Vienna - European Society of Human Genetics

Genetic analysis, linkage ans association
in Czech population.
However, many patients (about 50%) with a clinical diagnosis of FH
have no LDLR mutations identified by this approach. Part of the diagnostic
gap is attributable to the genetic heterogeneity of FH. Another
possible explanation is that mutation analysis using exon by exon
screening may fail to detect the mutant allele in case of large intragenic
rearrangements avoiding primer annealing in the deleted area. In order
to explore the possibility that whole exon deletions or duplications
could be the cause of the mutant phenotype, we used MLPA technique
in this study. Six different large deletions and three duplications were
found in Czech population.
We designed the APEX (arrayed primer extension) based genotyping
microarray for the simultaneous detection of 160 selected mutations
and 330 bp of resequencing area of the LDLR gene. The first validation
results indicate that the FH chip seems to be a suitable tool for the first
line screening of mutations in the LDLR gene.
This work was supported by grant MSMT 2B08060.
P17.50
mitochondrial DNA haplogroups and the risk of Parkinson
disease in a cohort of patients from south italy
V. Scornaienchi 1 , E. V. De Marco 1 , D. Civitelli 1 , F. Annesi 1 , P. Tarantino 1,2 , F.
E. Rocca 1,3 , V. Greco 1 , G. Provenzano 1,2 , C. Giordano 1 , W. Sproviero 1,3 , G. Annesi
1 ;
1 Institute of Neurological Sciences, National Research Council, Piano Lago di
Mangone, Italy, 2 Department of Neuroscience, Psychiatry and Anesthesiology,
University of Messina, Policlinico Universitario, Messina, Italy, 3 Institute of Neurology,
University of Magna Graecia, Catanzaro, Italy.
There is increasing evidence that European mitochondrial DNA (mtD-
NA) haplogroups J and K, and their shared 10398G single-nucleotide
polymorphism (SNP) in the ND3 gene, have a protective role in the
cause of idiopathic Parkinson’s disease (PD). We tested whether certain
polymorphisms in mtDNA can predispose to PD in a population
that is rather genetically homogeneous. Here, we determined the distributions
of these mtSNPs, the constructed haplogroups and the clusters
or superclusters of these haplogroups in a large cohort of 363 PD
patients (213 males and 150 females, age at onset ≥50) from South
Italy with idiopathic PD vs a group of 400 unaffected individuals from
the same geographyc area
In a preliminarily analysis we found no mtSNP or mtDNA haplogroup
that predisposes to PD in our South Italy population. Specifically our
results indicated that the distributions of the nine major European haplogroups
among South Italy PD patients did not differ significantly from
those of the surrounding European genetic landscape. In particular,
from the present study it can be deduced that no mtDNA variations
predisposing to PD are present in the South Italy population, and that
these results are in keeping with previous studies that failed to detect
causally related mtDNA sequence variations in this disorder.
P17.51
ceruloplasmin gene variations and Parkinson’s disease: an
association study in southern italian population
F. E. Rocca 1,2 , V. Greco 1 , F. Annesi 1 , P. Tarantino 1,3 , E. V. De Marco 1 , D. Civitelli
1 , G. Provenzano 1,3 , V. Scornaienchi 1 , W. Sproviero 1 , G. Annesi 1 ;
1 Institute of Neurological Sciences,National Research Council, Mangone
(Cosenza), Italy, 2 Institute of Neurology, University Magna Graecia, Catanzaro,,
Italy, 3 Department of Neurosciences, Psychiatry and Anaesthesiology University
of Messina, Messina, Italy.
Ceruloplasmin (CP) regulates iron levels in the central nervous system
and prevents free radical injury. Iron-related oxidative stress is an important
component of the neurodegenerative process in Parkinson’s
disease (PD). A possible involvement of ceruloplasmin in the pathogenesis
of PD has been supported by immunohistochemical studies
that reveal a colocalization of ceruloplasmin and Lewy bodies. It has
been reported that there are alterations in ceruloplasmin concentration
and ferrroxidase activity in serum from heteroallelic Pd patients.
Some functional findings show that altered activity of ceruloplasmin
may present a vulnerability factor for iron induced oxidative stress in
PD. To elucidate the role of this gene in our population, we screened a
total of 230 sporadic PD patients and 231 controls from Southern Italy
for the six know variations (I63T,P477L, D544E, T551I, R793H and
T841R) identified in a german population. All the patients were diagnosed
with idiopathic PD according to the UK brain bank criteria and
gave informed consent according to the declaration of Helsinki The
genetic screening was performed by direct sequencing of the coding
region of CP gene for four variations and by restriction analysis for the
other two variations. Each variation taken individually, did not show association
to PD and no significant differences were observed between
cases and controls. Our results do not support a possible association
between Cp variations and PD in Southern Italian population.
P17.52
Association study between HFE, tF, tFR genes and Parkinson’s
disease
V. Greco 1 , E. V. De Marco 1 , F. E. Rocca 1,2 , F. Annesi 1 , D. Civitelli 1 , G. Provenzano
1,3 , P. Tarantino 1,3 , V. Scornaienchi 1 , G. Annesi 1 ;
1 Institute of Neurological Sciences, National Research Council, Mangone
(Cosenza), Italy, 2 Institute of Neurology, University Magna Graecia, Catanzaro,
Italy, 3 Department of Neurosciences, Psychiatry and Anaesthesiology University
of Messina, Messina, Italy.
Iron overload increases oxidative stress and may lead to neurodegenerative
disorders like Parkinson’s disease (PD). Alterations of iron-related
genes, therefore, might be involved in the pathogenesis of PD.
The aim of this study was to investigate a possible association between
the polymorphisms C282Y and H63D of the haemochromatosis (HFE)
gene and the prevalence of PD in Southern Italy. These variants of the
HFE gene cause an iron overload disorder, known as hereditary haemochromatosis.
Contradictory evidence exists on the role of the HFE
variants as risk factors for PD. The HFE protein is thought to interact
with the transferrin receptor (TFR), lowering its affinity for iron-bound
transferrin (TF). Subsequently we also analyzed if the polymorphisms
G258S of the TF gene and S82G of the TFR gene are other risk factors
for PD. We examined those four polymorphisms in 181 sporadic PD
patients and 180 controls from Southern Italy. The clinical diagnosis
of PD was based according to the UK PD Brain Bank Society criteria.
We carried out a genetic analysis by standard PCR and restriction
digestion method. We did not find significant differences in genotype
and allele frequencies between PD and controls for all polymorphisms
studied. Our results suggest that the C282Y and H63D variants do not
contribute significantly to the risk of PD. Furthermore, there was no
association between the G258S TF gene and S82G TFR gene with
PD. However, it would be interesting to extend our study to other iron
related genes to verify their potential role in PD.
P17.53
sequence analysis of mtDNA in Parkinson‘s disease patients
from Bashkortostan Republic of Russia
I. Gilyazova 1 , I. Khidiyatova 1 , O. Derbeneva 2 , E. Ruiz-Pesini 3 , R. Khusainova 1 ,
R. Magzhanov 4 , D. C. Wallace 2 , E. Khusnutdinova 1 ;
1 Institute of Biochemistry and Genetics,Ufa Science Centre, RAS, Ufa, Russian
Federation, 2 Centre for Molecular and Mitochondrial Medicine and Genetics,
Irvine, CA, United States, 3 cDepartamento de Bioquimica, Biologia Molecular y
Celular, Universidad de Zaragoza-CIBERER-ISCIII, Zaragoza, Spain, 4 Bashkir
State Medical University, Ufa, Russian Federation.
MtDNA common variation is reported to modify the risk of Parkinson’s
disease (PD). We evaluated the impact of the mtDNA variant on PD
risk in 157 unrelated Tatar PD patients and 183 unrelated control subjects.
Whole mtDNA sequencing in two PD patients with haplogroup
H (H and H2) and two with haplogroup U (Uk1 and U4) PD patients
showed that haplogroup H mtDNA harbored one potentially functional
variant, tRNALys A8343G. The Tatar haplogroup H2 mtDNA harbored
another unusual variant, a homoplasmic ND2 gene missense mutation
(A64T, CI =82%), which could increase the risk of developing PD.
The haplogroup U mtDNAs, U4 and Uk1, both harbored the defining
haplogroup U tRNALeu(CUN) variant A12308G and the 16S rRNA
A1811G subhaplogroup U variant. They also shared common variants
A1438G in the 12S rRNA and A2706G in the 16S rRNA. The U4 mtD-
NA had the defining cytochrome b gene variant T15693C (M316T).
However, this mtDNA also harbored the rare ND4L missense mutation
at C10654T (A62V) (CI = 3%) and the polymorphic double missence
variant at T8567C in the ATP8/ATP6 gene overlapping region (S68P/
I14T) (CI = 23% and 33%, respectively). TheUk1 mtDNA had the defining
subhaplogroup polypeptide missence mutations ATP6 nt G9055A
(A177T), ND3 nt A10398G (T114A), and cytochrome b nt T14798C
(F18L). However, the Uk1 mtDNA also contained a heteroplasmic missense
mutation in the COII gene at nt G7637G/A (E18K) (CI = 100%).