2008 Barcelona - European Society of Human Genetics

Genetic counselling, education, genetic services, and public policy
community, has established the Genetic Testing Reference Materials
Coordination Program (GeT-RM) to improve public availability of reference
materials and facilitate information exchange and communication
on reference materials development, contribution, characterization,
distribution, and needs assessment . RESULTS: The GeT-RM has
characterized reference materials for Huntington disease, Fragile X,
cystic fibrosis, Bloom syndrome, familial dysautonomia, Canavan disease,
Niemann-Pick disease, Tay-Sachs disease, Gaucher disease,
glycogen storage disease type 1a, Fanconi anemia, and mucolipidosis
type IV . The GeT-RM program also collects information from other
sources about publicly available cell lines/DNA with clinically important
mutations that may be useful as reference materials . This information
is posted on the program website . To date, the GeT-RM has focused its
efforts on DNA based testing for inherited genetic disorders . However,
we hope to expand our efforts into other areas of genetics, including
molecular oncology and biochemical genetic testing . CONCLUSIONS:
The increased availability of characterized reference materials for quality
assurance, proficiency testing, test development and research, will
help to improve the quality and accuracy of genetic testing . GeT-RM
website: http://wwwn .cdc .gov/dls/genetics/rmmaterials/default .aspx
P09.63
The role of AZFc region microdeletion in repeated pregnancy
loss
S. M. Kalantar1 , M. H. Sheikhha1 , H. Fazli1 , M. Solimani1 , F. Pakravesh2 ;
1 2 Research & Clinical Centre for Infertility, Yazd, Islamic Republic of Iran, Aban
Hospital, Tehran, Islamic Republic of Iran.
Objective: To evaluate the role of Y chromosome microdeletion in the
case of couples had problem with repeated pregnancy loss (RPL) ingroup
of unknown cause compared with couples with male factor infertility
.
Materials & Methods: A controlled clinical study was desgined in our
centre . In total, 100 men from male factor infertility and 25 men with
RPL were recruited in the study .
DNA was extracted from Peripheral blood sample . In each sample,
six sequence-tagged-sites (STS) according to the europian protocol
and four other STSs in the proximal AZFc region namely; DYS262,
DYS220, DYF8551, and DYF8651 were studied by polymerase chain
reaction (PCR) .
Results: Eight men tested evaluated had Y microdelation in at least
one of the six segments from Europian protocol (8%) VS non in RPL
group . Five men with history of at least 3 PL in their wife tested for 4
STS in AZFc region had microdelation (20%) but non of those other
STS . In the inferile group had not any microdeletion related to the 4
STS from AZFc region .
Conclusion: From our results it could concluded that in case of couples
with un explained PRL it may help to test these four STSs on Y chromosome
to recognize the cause of PL .
P09.64
mutational homogeneity of severe autosomal recessive retinal
degeneration in endogamous Romany (Gypsy) communities in
slovakia
A. Ficek 1,2 , E. Feráková 1 , L. Kádaši 1,2 , G. Minárik 1 , H. Poláková 2 , V. Ferák 1 ;
1 Comenius University, Faculty of Natural Sciences, Bratislava, Slovakia, 2 Slovak
Academy of Sciences, Institute of Molecular Physiology and Genetics,
Bratislava, Slovakia.
Hereditary retinal degenerations comprise clinically and genetically
wide group of mostly progressive ocular disorders and are one of the
most frequent causes of vision impairment in developed countries . So
far uncovered tremendous genetic heterogeneity underlying majority
of these disorders however markedly impedes ongoing attempts
on DNA diagnostics and therapy in most of populations . Contrary to
panmictic populations, genetic heterogeneity in isolated populations
is often reduced to high degree due to founder effect and inbreeding .
Severe childhood autosomal recessive rod-cone progressive retinal
degeneration with feature of retinitis pigmentosa (nyctalopia, dark pigment
formations, attenuated retinal vessels) and nystagmus characteristic
for LCA phenotype occurs in higher frequency in to the high
degree isolated Romany communities in Slovakia . Whole genome autozygosity
mapping and linkage analysis accomplished on analysis of
two large pedigrees facilitated localization and identification of underlying
mutation to which bidirectional allele specific amplification method
was designed for routine mutation detection . Geographically delimited
occurrence of the disease confirmed community structure of Romany
population with existence of small, endogamic founder settlements .
Growing of such small communities, characterized by high consanguinity
rate, results in markedly increased incidence of this autosomal
recessive disorder in some regions leading to significant genetic burden
to the population . While no effective therapy exists for the disorder
at the moment, cascade carrier screening and genetic counseling
proffered to the families is currently the only possible approach to the
management of the disease .
P09.65
Governing the balance between ‘duty to protect’ and ‘right to
test’ ii: New forms of protection in genetic screening
M. C. Cornel, T. Pieters, C. G. van El;
VU University Medical Centre, Amsterdam, The Netherlands.
While in the previous century the availability of genetic testing and
screening was governed by public health authorities and medical professionals,
increasingly direct-to-consumer tests become available .
While on the one hand people have become more free to decide for
themselves whether they want to order their genetic risk test, on the
other hand, lack of counselling, personalized advice resembling general
lifestyle advice or incorrect results may lead to disappointment or
may prove harmful . Quality of genetic services is no longer guaranteed
by existing regulations .
In the United Kingdom the Human Genetics Commission has updated
its recommendations concerning direct-to-consumer testing, calling for
stricter control, without precluding commercial testing, for instance by
recommending that the test be offered by a qualified health professional
.To guarantee informed decision making, the public needs to
have access to high quality information (trusted websites) . Education
and communication are needed to inform the public at large on pros
and cons of genetic screening . Policy makers should engage with patient
and consumer organisations . Especially for complex diseases
translational research is needed . Possibilities to regulate marketing of
commercial test offers after adequate pre-market evaluation need to
be debated and implemented. The European certificate CE marking
should guarantee analytical validity and clinical validity . Assessment
of clinical utility, relating to the availability of effective interventions,
should be performed for new forms of testing and screening for lowrisk
populations and high as well as low-risk gene variants .
P09.66
Governing the balance between ‘duty to protect’ and ‘right
to test’ i: challenges to the focus on protection in genetic
screening
C. G. van El, T. Pieters, M. C. Cornel;
VU University Medical Centre, Amsterdam, The Netherlands.
For genetic screening, criteria have been developed based on the
WHO Wilson and Jungner criteria (1968), in which the notion of protection
of citizens against unwarranted screening was important . In
some countries, such as the Netherlands, ‘protection’ even became
cornerstone of legislation concerning population screening . Protection
relates to notions of having a suitable test with good sensitivity and few
false positives, the availability of treatment and follow-up after diagnosis,
so that benefits of screening outweigh potential harm, for instance
of stress caused by uncertainty, the knowledge of having a fatal disorder
or unnecessary interventions .
In screening policy safeguards are needed because of the shared responsibilities
of government and health care taking the initiative to offer
screening to - in principle - healthy people .
We argue that recent developments challenge this protective stance .
Firstly, on the basis of developments in genomics, among other association
studies, labs and companies increasingly offer direct-to-consumer
tests on the internet . Secondly, there is increasing awareness
about and demand for testing and screening, sometimes stimulated
by patient organisations . For instance, in the Netherlands, parents of
children with Duchenne Muscular Dystrophy argue that people might
want a newborn screening test for DMD to be able to prepare or make
reproductive decisions .
The emphasis on protection ignores increasing demands for testing .
Citizens want to be more autonomous . “Informed decision making” is
not taken seriously when many genetic screening tests are simply not