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

Genetic analysis, linkage, and association
P0966. Novel gene loci for the Enlarged Vestibular Aqueduct
Syndrome
R. Birkenhäger, K. Jaekel, R. Laszig, A. Aschendorff;
University, Freiburg, Germany.
Background: Enlarged Vestibular Aqueduct Syndrome (EVA-Syndrome)
(MIM 603545) is the most common form of congenital inner
ear abnormality seen in radiological assessment, associated with sensorineural
hearing impairment or syndromic forms of deafness such
as Pendred syndrome (MIM 274600). Up to now only mutations in
the SLC26A4 gene, located on Chromosome 7q31, have been made
responsible for Pendred- and EVA-Syndrome. This gene product, a
transporter of iodide and chloride, is called pendrin. In this study we
analyzed 64 patients with EVA and hearing loss to distinguish between
the Pendred- and EVA-syndrome.
Methods: Individual exon and intron transitions of the SLC26A4 gene
of patients were PCR amplified. Direct automatic sequencing of variant
fragments was performed with the same primers. A genome-wide
linkage analysis was accomplished using the Affymetrix 10K/50K XbaI
SNP GeneChip® mapping array.
Results: In the analysed patient collective with Pendred syndrome
and/or enlargement of the vestibular aqueduct, a total of eighteen
SCL26A4 mutations were detected. A mutation could not be detected
in 36 % of the cases. With a genomewide linkage analysis, of these
families, using SNP technology, it was possible to identify potential
new gene loci for the EVA-Syndrome.
Conclusions: The novel gene loci will be analyzed for additional genes
involved in the development of the EVA-Syndrome. Our results indicate
evidences of a accessory gene for this Syndrome.
P0967. Clinical and genetic familial study of 61 children showing
different epileptic phenotypes
R. Combi 1 , S. Redaelli 2 , D. Grioni 3 , M. Contri 2,3 , D. Barisani 4 , M. L. Lavitrano 5 ,
G. Tredici 2 , M. L. Tenchini 6 , M. Bertolini 2,3 , L. Dalprà 2 ;
1 Dept. Biotechnologies and Biosciences, University of Milano-Bicocca, Milano,
Italy, 2 Dept. Neurosciences and Biomedical Technologies, University of Milano-
Bicocca, Monza, Italy, 3 Infantile Neuropsychiatry Clinic, S Gerardo Hospital,
Monza, Italy, 4 Dept. Experimental Medicine, University of Milano-Bicocca, Monza,
Italy, 5 Dept. of Surgical Sciences and Intensive Therapy, University of Milano-Bicocca,
Monza, Italy, 6 Dept. Biology and Genetics for Medical Sciences,
University of Milano, Milano, Italy.
During the last 10 years many advances in the genetics of epilepsies
have been done. In particular, several mutations have been detected
in genes encoding ion-channels, suggesting that epilepsies are “channelopathies”.
Nevertheless, the genetic basis of idiopathic epilepsies
remain unknown for a large number of cases and the genetic transmission
of these diseases appear to be “complex” because of the great
genetic heterogeneity and the coexistence of different epileptic types
in each familial cluster. Moreover, in different epilepsies, mutations in
the same gene have been reported.
We performed a clinical and genetic study on 60 Italian families (61
probands) showing idiopathic epilepsies by sequencing DNA regions
previously associated to epilepsies in order to collect data on the type
and frequency of ion channel mutations. Partial epilepsies represented
28% of the sample, whereas the remaining 72% was constituted by
generalised epilepsies, subdivided in myoclonic (JME, BMEI, MAE,
SMEI) and non-myoclonic (GEFS+, GTCS, CAE, FS) epilepsies.
We observed a genetic complexity in all phenotype groups: any epileptic
type may be transmitted in either an autosomal dominant or a recessive
manner, and furthermore even within a single family, epilepsy
can be transmitted in either manner.
No significant phenotype identity among generations was observed.
Moreover, we found an excess of transmitting mothers but no differences
in the sex of children, suggesting a possible role of mitochondria
in the disease pathogenesis. The frequency of known mutations in the
analyzed regions resulted very low, while a new missense mutation in
SCN1A was identified in one subject.
P0968. The analysis of association of six polymorphisms with
development of ESRD in Romanian population - a preliminary
report
D. Cimponeriu 1 , P. Apostol 2 , D. Ungureanu 3 , C. Moldovan 3 , A. Craciun 1 , C. Serafinceanu
1 , D. Usurelu 2 , M. Stavarachi 2 , M. Toma 2 , L. Cherry 1 , L. Dumitrescu 2 ,
P. Cimponeriu 1 , L. Gavrila 2 ;
1 2 N Paulescu Institute, Bucharest, Romania, Institute of Genetics, Bucharest,
Romania, 3Titu Maiorescu University, Bucharest, Romania.
Diabetic nephropathy is the leading cause of ESRD. The literature
suggests that genetic predisposition to ESRD is very complex.
In this study we assessed the association of six polymorphisms with
ESRD in Caucasian subjects from South part of Romania.
We analyzed blood samples from unrelated dialyzed patients (etiology:
T1DM: 83, T2DM: 87, chronic glomerulonephritis: 84) and healthy controls
(n=494). Six genes polymorphisms associated with extracellular
matrix proliferation (HSPG BamH1, TGF-beta-509C/T) or regulation
of blood flow and vascular function (ACE ID, AGTR1, eNOS, MTHFR)
were genotyped by PCR or PCR - RFLP. Genotype distribution for both
cases and controls is in respect with Hardy-Weinberg equilibrium for
all studied polymorphisms.
Our results showed that eNOS ID polymorphism increases the risk
for ESRD in all groups. The highest value was observed in T1DM patients
(OR :3.9844, CI95%:1.9198