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

Genetic analysis, linkage, and association
breast cancer alone are not caused by mutations in BRCA1 or BRCA2
(BRCAX families). Unfortunately, the discovery of additional breast
cancer predisposition genes has so far been unsuccessful, presumably
because of genetic heterogeneity, low penetrance, and/or recessive/polygenic
mechanisms.
Material and Methods: With the aim of finding breast cancer predisposition
genes, we genotyped 6000 SNPs across the genome using a
high-throughput technology (Illumina Linkage panel IV), in 41 BRCAX
families from Spanish population. SNP data analysis has been performed
using the new version of Merlin (MERLIN v.0.10.2) to model
marker-marker linkage disequilibrium in order to avoid artefacts due
to LD among SNPs.
Results: These data analysis have allowed us to identify two regions
with suggestive linkage (Dominant Parametric LOD score ~ 2.3, alpha
~0.3) in chromosomes 3q and 6q, and one region with complete linkage
(Dominant Parametric LOD score > 3.2, alpha ~0.5) in chromosome
21q. In order to confirm these regions, and narrow them if possible,
we are genotyping 2 cM density microsatellite map within them.
P0971. Cardiovascular symptoms associated with mutations in
the genes encoding fibrillin-1 (FBN1) and transforming growth
factor beta receptor type II (TGFBR2)
S. Waldmüller1 , M. Müller1 , H. Warnecke2 , W. Rees2 , W. Schöls3 , G. Walterbusch4
, J. Ennker5 , T. Scheffold1 ;
1 2 University of Witten Herdecke, Dortmund, Germany, Heart Centre Osnabrück-
Bad Rothenfelde, Bad Rothenfelde, Germany, 3Heart Centre Duisburg, Duisburg,
Germany, 4St.-Johannes-Hospital Dortmund, Dortmund, Germany, 5Heart Centre Lahr/Baden, Lahr (Baden), Germany.
Objectives: Mutations in the genes encoding fibrillin-1 (FBN1) and
transforming growth factor beta receptor type II (TGFBR2) are known
causes of Marfan syndrome (MFS) and related disorders. The objective
of the present study was to assess whether the type of mutation is
linked to a particular clinical subtype of the cardiovascular condition.
Methods: The genetic and clinical records of 36 patients referred to
us for molecular genetic diagnosis were reviewed. The frequency of a
number of clinical signs was determined for the following three groups
of patients: 1. carriers of a FBN1 mutation that affects a Ca2+-binding
epidermal growth factor-like domain (cbEGF); 2. carriers of a mutation
associated with a premature termination codon, PTC, in FBN1; 3. individuals
with no mutation detected in either FBN1 or TGFBR2.
Results: Throughout the study cohort, the incidence of aortic dissections
per se did not depend on the type of mutation. However, we found
that mutations affecting the calcium-binding epidermal growth factorlike
domain were more frequently associated with a dissection of distal
parts of the aorta than mutations that lead to a premature termination
codon (χ2 : p=0.013), suggesting that the spatio-temporal pattern of
1
vascular deterioration may vary with the type of mutation.
Conclusion: Routine genetic testing of patients with suspected MFS or
thoracic aortic aneurysms/dissections could provide further insight into
genotype/phenotype correllations related to aortic dissection.
P0972. Fragile X syndrome screening in families with
consanguineous and nonconsanguineous marriages in the
Iranian population
S. S. Abedini 1 , K. Kahrizi 1 , R. Kariminejad 2 , V. Hadavi 2 , F. Behjati 1 , N. Mansoorian
2 , N. Nikzat 1 , S. Esmaeeli Nieh 3 , S. Banihashemi 1 , S. N. Almadani 2 , F.
Afroozan 2 , Y. Shafeghati 1 , A. Tzschach 3 , A. Kuss 3 , H. H. Ropers 3 , H. Najmabadi
1,2 ;
1 Genetics Research Centre, University of Social Welfare and Rehabilitation
Sciences, Tehran, Islamic Republic of Iran, 2 Kariminejad-Najmabadi Pathology
and Genetics Center, Tehran, Islamic Republic of Iran, 3 Max Planck Institute for
Molecular Genetics, Berlin, Germany.
Fragile X syndrome is the most common form of inherited mental retardation
(MR). It is caused by the expansion of CGG triplet repeats in the
fragile X mental retardation 1 (FMR1) gene. Normal individuals have