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

Genetic counselling, education, genetic services, and public policy
P1392. Neuropsychological and Behavioural profile in
adolescents and young adults with Smih-Magenis syndrome
K. Hernandez 1 , M. T. Le Normand 2 , H. de Leersnyder 1 , A. Verloes 1 ;
1 Department Genetics, PARIS, France, 2 INSERM, PARIS, France.
Smith-Magenis syndrome (SMS) is a multiple congenital anomalies
and mental retardation syndrome associated with an interstitial deletion
of chromosome 17 band p11.2. Six adolescents (3 boys and 3
girls aged 12 to 15 years) and 4 adults (3 boys and 1 girl aged 19 to
22 years) with SMS were administered a cognitive battery including
a neuropsychiatric and a behavioural scale for measuring Intellectual
efficiency (PEP-R, EDEI-R, WAIS) Neuropsychiatric Inventory (NPI),
Social maturity and Autonomy (Vineland Adaptative Behaviour Scale).
The results demonstrate a mild-to-moderate range of mental retardation
of all patients, (IQ for young adults ranged from 44 to 64), without
any discrepancy between verbal and performance scales.
Adolescents show impulsive and unstable behaviors with agitation/
mood instability, auto and hetero-aggressivity which interfered with
learning and social variables. Intellectual efficiency is underestimated.
Sociocultural level is a strong factor to understand the pattern of their
cognitive profile. Scores on logical reasoning and working memory are
poor. Moreover, speed of information processing is very impaired.
Adults were so impulsive that they could not inhibit a contrary action.
Concerning sexual behavior, desinhibition is very frequently reported
by the families.
Motor instability remained important but the mood instability was more
adaptive. 3 out of 4 young adults have episodes of fabulation but none
have any depression.
Such results show evidence that stimulations for speaking and learning
are crucial in adolescents and young adults with SMS and should
be carried on. Their needs are still educational and have strong implications
for their cognitive abilities and autonomy.
P1393. Molecular diagnosis of Egyptian patients with spinal
muscular atrophy
M. L. Essawi, G. M. M. Al-ettribi, A. A. El-Haroni, L. Effat, K. S. Amr, S. Ismail,
Y. Z. Gad;
National Research Center, cairo, Egypt.
Childhood spinal muscular atrophy (SMA) is one of the most common
autosomal recessive disorders. It is characterized by symmetrical
muscle weakness and atrophy of limbs and trunk. It has an estimated
incidence on 1:6000 live births and a carrier frequency of 1:50 individuals.
Childhood SMA is classified into 3 types (I, II and III) according to
the age of onset and the clinical severity.
This study aimed to characterize the molecular basis of SMA among
Egyptian patients.
Eighty two Egyptian patients were clinically diagnosed as SMA, they
were classified into 32 type I, 36 type II and 14 type III cases. Detection
of homozygous absence of exons 7 and 8 of SMN1 gene was carried
out using the PCR-restriction digestion method, whereas, deletion of
NAIP exon 5 was detected through multiplex PCR.
Homozygous absence of SMN1 gene exon 7 and 8 or exon 7 only was
found in 69.4% of all patients. Of these patients, exon 5 of NAIP gene
was deleted in 78% of type I, 34.3% of type II, and 28.6% of type III.
The molecular basis of SMA in Egyptian is almost similar to that reported
by other ethnic groups. The PCR-restriction digestion method
is fast, accurate and reliable for direct diagnosis of SMA and it could be
used efficiently for genetic counseling. Studying the presence of compound
heterozygous and homozygous point mutations in SMN1 gene
is recommended in the non-deleted SMA patients (approx. one third).
P1394. Cardiac genetic services - Ascertaining individuals at risk
of a sudden cardiac death syndrome
S. J. Collitt1 , B. Kerr1 , W. Newman1 , J. Clayton-Smith1 , K. Strong2 , P. Griffiths1 ,
K. Metcalfe1 ;
1Central Manchester & Manchester Children’s University Hospitals NHS Trust,
Manchester, United Kingdom, 2Nowgen, Manchester, United Kingdom.
Purpose: An audit of referrals to the North West Regional Genetic Service
(population 4.3 million) in 2004, showed that 24 patients had been
referred to Clinical Genetics with a personal or family history of a Sudden
Cardiac Death (SCD) syndrome e.g. long QT syndrome, Brugada
syndrome or a cardiomyopathy. Statistically there are approximately
12,000 patients in Greater Manchester alone with these conditions.
Clearly this patient group is under-represented in genetic services sug-
gesting a large unmet need.
In order to determine the optimum method of increasing appropriate
referrals to Clinical Genetics, a two year service development project
was designed looking at three different referral methods, across the
three cardiac tertiary centres in the North-West.
Findings: The project has demonstrated that the most effective way of
increasing appropriate referrals has been the presence of the cardiac
liaison nurse in cardiology clinics and on the wards. This has resulted
in a 454% increase in referrals to 109 in the first year of the project. An
audit of 61 referrals has shown an average of 5 surviving first degree
relatives per pro band. The project has therefore identified approximately
545 at risk relatives.
The nurse has also been able to identify barriers to referrals and ways
of overcoming them.
Conclusion: Increasing appropriate referrals to clinical genetics has enabled
the identification of family members at risk of a SCD syndrome.
This has facilitated the provision of genetic counselling, genetic testing
and cardiac assessment of these family members, thereby reducing
the risk of Sudden Cardiac Death.
P1395. Partnering to develop orphan drugs : evaluation of
OrphanXchange services
V. Thibaudeau 1 , J. McGregor 2 , C. Holef 2 , A. Dubosq 2 , B. Urbero 2 , S. Aymé 2 ;
1 Inserm sc11, paris, France, 2 Inserm sc11, Paris, France.
The OrphanXchange project started in the context of a FP6 European
contract called OrphanPlatform. One of the aims of this project was the
development of information tools to allow a comprehensive and integrated
approach for addressing the set of factors that currently affects
translational research in the field of rare diseases and orphan drugs. A
database of ongoing research projects was set up in the context of Orphanet
and a specific website, www.orphanxchange.org, was created
to facilitate the formation of partnership activities between academic
scientists and industry. The website provides free access to research
projects that scientists wish to develop in partnership with industry. For
industry, it is a database of business opportunities. Although minimal
information is provided freely, more detailed information is only accessible
after registration, which allows identification of the customers.
Customers only have access to the scientist’s details if they make a
contact request. Currently, the database includes 129 projects. The
site is visited 500 times per month. Half of the 213 registered users are
from industry (biotech, big pharmas, consultants, investors), and the
other half are from academia. These members are from 31 countries,
the largest number of users coming from France, Japan, the USA,
and Sweden. In two years, 113 requests to make contact with a researcher
were received. Three partnership projects were successfully
developed thanks to the service. The plan is to extend this service to
cover requests for partnership between academic teams, and between
industry teams (for example, small SMe and big pharma).
P1396. A procedure for validation, verification and follow-up of
methods in an accredited genetics laboratory
I. Bouchardy, I. Moix, C. Hinard, M. A. Morris;
Service of Genetic Medicine, University Hospitals, Geneva, Switzerland.
Test validation, defined as “confirmation, through the provision of objective
evidence, that the requirements for a specific intended use or
application have been fulfilled” is a necessary element of quality assurance
and a requirement for laboratory accreditation.
Both new methods and modifications that may influence the quality
of the results must be validated before diagnostic use. For practical
reasons, the intensity of validation must be adapted for different procedures
- laboratories should define for each test the elements to validate
that are necessary and sufficient.
Validation, the more thorough procedure, requires test-based confirmation
of precision (repeatability and reproducibility), sensitivity, specificity
and ruggedness. It is applied for example to new technologies, or
in case of major technical modifications to existing methods, or when
the performance of installed methods is insufficient.
Verification (or “implantation validation”) is a less intensive procedure,
typically employed in case of minor technical modifications or additions,
or when implanting a diagnostic kit that has been validated by an
external company or laboratory. Examples include changing a primer
sequence in a PCR reaction or an enzyme for digestion, or adding an
additional exon to an existing sequence-based test.