2009 Vienna - European Society of Human Genetics

Genetic counseling Genetics education, Genetic services, and Public policy
P01.45
Rhombencephalosynapsis and related anomalies: the largest
fetal series lead to suggest a European network.
L. Pasquier 1,2 , C. Bendavid 3,2 , C. Evain 2 , I. Gicquel 2 , P. Loget 4 , C. Dubourg 3,2 , S.
Jaillard 5,2 , S. Mercier 1 , A. Laquerrière 6 , V. David 3,2 , S. Odent 1 ;
1 Medical Genetics, Rennes, France, 2 UMR6061 CNRS, Rennes 1 University,
Rennes, France, 3 Molecular Genetics Lab, Rennes, France, 4 Pathology Lab,
Rennes, France, 5 Cytogenetics Lab, Rennes, France, 6 Pathology Lab, Rouen,
France.
Rhombencephalosynapsis (RS) is a rare cerebellar malformation defined
by vermian agenesis with fusion of the hemispheres and the dentate
nuclei. Embryologic and genetic mechanisms are still unknown
and to date , no animal models are available.
We have created a RS database to carefully review the phenotype
observed in France including familial, clinical, radiological and pathological
patterns. The morphological analysis of 40 foetuses (Pasquier
et al., 2009, Acta Neuropathol 117: 185-200) allowed us to confirm
that RS is always associated with other brain abnormalities and can
be classified into three groups : 1- pure neurologic forms from isolated
RS with hydrocephalus to supratentorial midline abnormalities
(neural tube defect or holoprosencephaly), 2- syndromic forms with
VACTERL-H association, 3- other syndromic conditions (Gomez-Lopez-Hernandez
syndrome).
We have also collected several postnatal cases without hydrocephalus
or severe neurological symptoms. This might suggest that RS is underdiagnosed
during prenatal or postnatal periods (less than 80 cases
reported in the litterature). In order to precise its frequency, neurological
prognosis and genetic counselling, we intend to create a European
network to gather most of the rhombencephalosynapsis cases and
share the results provided.
From DNA samples collected, this survey would also aim at looking
for genetic factors using a pangenomic screening tool (CGH-array).
This approach has already enabled us to identify 2 different microrearrangements
from a series of 20 cases. Contact: laurent.pasquier@
chu-rennes.fr
P01.46
should we screen for gene mutations in blood samples with
mcH greater than 27pg in areas with a high prevalence of
thalassaemia?
N. Saeidi, M. Jafarinejad, E. Shafieie, M. Mohammadi, M. Taghavi, F. Bayat, M.
Karimi pur, A. Kordafshari, S. Zeinali;
pateur Institution, Tehran, Islamic Republic of Iran.
Screening strategies for thalassaemia carriers are usually based on
cut off values for red blood cell indices (either MCV or MCH).There
is evidence for a higher sensitivity for MCH 27
pg.
Blood samples from 36 individuals with MCH greater than 27pg (MCV
and Hb A 2 is normal too) were screened for presence of globin gene
mutations and α globin gene deletions by ARMS PCR, Sequencing
and Multiplex gap PCR.
Twelve individuals harbored globin gene mutations. Of these, 3 had
HbS, 2 had HbD, 2 had Cd75 mutations and 2 had deletions of one
α globin gene. Three individuals have β thalassaemia major; that we
believe because of transfusion these indices is normal.
If one partner is found to be a carrier of a β thalassaemia mutation or
single α gene deletion, it is advisable to look for HbS or α globin gene
deletions in the other partner, even if MCH and MCV is within normal
range.
P01.47
How do neurologists explain genetic causes of sporadic adultonset
ataxia to patients ?
Y. Ohnuki1 , A. Kondo1 , S. Izumi1 , M. Mizoguchi2 , S. Takagi1 ;
1 2 Tokai University School of Medicine, Kanagawa, Japan, Tokai University
School of Health Sciences, Kanagawa, Japan.
The etiology of sporadic adult-onset ataxia is poorly understood, but
Abele et al. reported that 13% of patients with negative family history
have causative genetic mutations. We found two patients with SCA3
mutation, who had a history of a family member(s) having been diagnosed
with sporadic ataxia several years earlier.
We studied how Japanese neurologists explained the genetic causes
of sporadic ataxia to patients by referring to the clinical records. At
the neurology clinic of Tokai University Hospital, 109 patients have
been diagnosed with spinocerebellar degeneration (SCD) since 1990.
Among them, 37 patients (34%) had positive family histories. Among
the 72 patients with sporadic ataxia only 16 patients had received a
clear explanation of the genetic causes from doctors, and 8 patients
had received genetic tests (SCA1, 2, 3, 6, 17, DRPLA). Although no
genetic mutations were found among sporadic ataxic patients who
took these tests, mutations might have been present among those
who did not take the tests. Family history may be negative because of
early death or late onset of parents, failure to diagnose SCD patients
among family members, reduced penetrance of the mutant allele, or
a de novo mutation for autosomal dominant ataxic gene. Neurologists
should consider possible genetic causes of sporadic ataxia.
P01.48
Challenges in guiding first year medical students in a one
semester genetic journey
R. M. Dragotoiu, L. C. Bohiltea;
Medical and Pharmacy University “Carol Davila”, Bucuresti, Romania.
Teaching is considered a well defined activity, which helped us all
achieve our knowledge, as also did our predecessors, and as, we assume,
will have to do our followers. Changes in everyday life, technology
development, but also changes in human mentality and/or view of
life, modified expectations in students as well as in teachers.
The dynamics of the teaching process is still under study and consensus
has not yet been reached on exactly what teaching techniques
should be used, to deliver the information and help students reach
knowledge on specialty aspects that might suit their own future medical
practice. Genetics is studied only in the first year at the Medical and
Pharmacy University “Carol Davila”, generating questions on the level
at which it should be taught.
Different questionnaires about the practicals were answered by 90
Romanian and 38 foreign students. The last group was again divided
because 15 students started later, had two practicals/ week instead of
the usual one, and had only one assistant lecturer, who also evaluated
them at the end of the practicals. Also 38 foreign students, some of
which were also in the groups which received questionnaires about the
practicals, were asked about the quality of 6 from 16 lectures.
After analyzing the results one can conclude the necessity of a better
connection between lectures and practicals, the latter having to loose
the mostly theoretical topics, genetics being a proper field for applying
different teaching methods even if students have various biology background
knowledge from high-school.
P01.49
Development of timely and relevant training courses for
healthcare professionals and genetic researchers
M. J. Leech 1,2 , F. Salway 3 , F. Jury 3 , P. Day 3 , D. Carthy 3 , L. Gaunt 4 , S. Hamilton 4 ,
A. Wallace 5 , R. Elles 5 , D. vanGent 5 , A. Devereau 5 , J. Crolla 6 , M. Bottomley 2 , K.
Mathieson 1,2 , W. Ollier 3 , M. Yuille 7 , D. Donnai 1,2 , H. R. Middleton-Price 1,2 ;
1 Nowgen - A Centre for Genetics in Healthcare, Manchester, United Kingdom,
2 Regional Genetics Service and Medical Genetics Research Group, Central
Manchester University Hospitals NHS Foundation Trust & University of Manchester,
Manchester, United Kingdom, 3 Centre for Integrated Genomic Medical
Research, University of Manchester, Manchester, United Kingdom, 4 Regional
Cytogenetics Unit, St Mary’s Hospital, Manchester, United Kingdom, 5 National
Genetics Reference Laboratory and Regional Genetics Service, St Mary’s Hospital,
Manchester, United Kingdom, 6 National Genetics Reference Laboratory,
Wessex, Salisbury, United Kingdom, 7 UK DNA Banking Network, Centre for
Integrated Genomic Medical Research, University of Manchester, Manchester,
United Kingdom.
Techniques for analysing genetic variants related to disease and treatment
are constantly advancing, and allow ever more sophisticated and
rapid analysis of patient samples. The consequence of greater access
to these techniques is that many clinical and laboratory disciplines
have to embrace the new technology.
Nowgen, A Centre for Genetics in Healthcare, in collaboration with
leading research and clinical scientists, has developed a portfolio of
accredited training courses for genetics professionals involved in research
and/or in the provision of clinical services. These courses have
been developed following a thorough consultation with senior clinical