2009 Vienna - European Society of Human Genetics

Laboratory and quality management
These results reveal a tendency for quality improvement in laboratories
participating in continuous education and EQA, which should lead
to improved services and patient care.
P15.11
Quality assurance and management in clinical cytogenetics
laboratories: the role of a technical assessor
B. B. Ganguly;
MGM Centre for Genetic Research & Diagnosis, Navi Mumbai, India.
Obtaining accreditation from reputed organization has become a concern
of many clinical cytogenetics laboratories across the world for
assuring a standard operating system. For clinical laboratories ISO
15189 standard is generally followed for accreditation. The technical
assessors in the field recruited by the accreditation organization assess
the quality system and documents of laboratory-operation with
the help of the check-list which is specifically designed by the accreditation
organization for the purpose. It has been experienced that the
experts engaged in routine or molecular diagnostic service with some
exposure in the field of clinical cytogenetics are employed for assessment.
However, such assessors fail to detect the diagnostic errors and
make specific comments on the inaccurate ongoing system and its
further improvement. It is true that conventional cytogenetics depends
on skilled expertise and dedicated involvement for extraction of correct
information on the constitutional or acquired anomalies and making
diagnostic interpretation on the present status and its future implication.
Involvement of inexperienced persons at technical and/or supervisory
level in lab operation and assessment as well will misinterpret
the standard of service and accreditation. The technical assessor shall
be a qualified expert with enough experience in clinical cytogenetics.
Failing which the accreditation might help the audited laboratory to
increase the work-load/business; however, the quality of diagnosis will
be compromised in such accredited laboratories. It is true that the constitutive
errors cannot be corrected, but accurate result can prevent the
recurrence of anomalies, while acquired anomalies can be treated in
many cases of hematological malignancies.
P15.12
EuroGentest: A collaborative network aimed at improving the
quality of genetic testing
R. J. Hastings 1 , D. E. Barton 2 , S. Berwouts 3 , C. Brady 2 , J. Camajova 4 , P. Corbisier
5 , A. Corveleyn 6 , L. Desmet 3 , R. Elles 7 , B. Fowler 8 , D. Gancberg 5 , R. T.
Howell 1 , T. Janssens 3 , O. Kamarainen 7 , M. J. Macek 4 , G. Matthijs 3 , M. A. Morris
9 , C. R. Müller 10 , N. Nagels 3 , G. Peirelinck 8 , B. Quellhorst-Pawley 1 , A. Stambergova
4 , E. Swinnen 3 , E. Dequeker 3 ;
1 John Radcliffe Hospital, Oxford, United Kingdom, 2 Our Lady’s Children’s
Hospital, Dublin, Ireland, 3 University of Leuven, Leuven, Belgium, 4 Charles
University, Prague, Czech Republic, 5 Institute for Reference Materials and Measurements,
Geel, Belgium, 6 University of Leuven,, Leuven, Belgium, 7 St Mary’s
Hospital, Manchester, United Kingdom, 8 University Children’s Hospital, Basel,
Switzerland, 9 University Hospital Geneva, Geneva, Switzerland, 10 University of
Würzburg, Würzburg, Germany.
EuroGentest, a European Commission funded Network of Excellence,
aims to improve and harmonize the quality of genetic testing (GT)
across Europe. EuroGentest includes a Quality Management (QM)
Unit whose main objective is to ensure that all genetic testing services
are offered within a structure that will assist Governments, regulators
and professional bodies to fulfil their responsibility to the public.
The Quality Management Unit has:- (1) organized 13 quality workshops
for genetic laboratories, covering 5 topics, where participants
learn about the requirements of a QM system and share experience
of problem-solving; (2) set up a database listing tests, accreditation
status and EQA participation of laboratories, enabling users to find
accredited laboratories and specific genetic tests (www.orpha.net);
(3) increased the range of EQA schemes available for CEQA, EMQN
& ERNDIM, organized meetings of EQA scheme organizers - consequently
some harmonisation and merging of EQA schemes has
occurred; (4) through workshops developed and produced diseasespecific
best practice guidelines; (5) produced draft guidelines for the
validation of assays for clinical use and DNA extraction and MLPA protocols
have been validated and (6) provided guidance on the proper
use of reference materials (RMs) with a priority list drawn up and RM
producers have been assisted with sourcing patient materials, design
of RM panels, validation of materials and the adoption of the Fragile
X RMs by WHO.
EuroGentest’s efforts have led to an increased awareness of the importance
of quality assurance in GT, and the projects are helping to
improve the quality of GT across Europe.
P15.13
Genetic testing in Europe: major differences from one country
to another
M. Jovanovic 1 , I. Caron 1 , E. Dequeker 2 , L. Desmet 2 , M. Morris 2 , J. Cassiman 2 ,
S. Aymé 1 ;
1 ORPHANET, PARIS, France, 2 EuroGentest, LEUVEN, Belgium.
Genetic tests are now offered internationally, through both public and
private sector genetic testing services. Physicians prescribing these
tests and biologists receiving the samples need to know which tests
are available, where they are performed and whether the identified
laboratories meet quality standards. To fulfil this need, www.orpha.net
was launched ten years ago to set up a database of clinical laboratories
in the field of rare diseases. The data collection covered 1 country
in 1997, 15 in 2003, 26 in 2006 and 38 in 2009. This major effort
was enabled thanks to resources from the EC DG for public health.
In collaboration with the EuroGentest NoE, information on quality
management has been added over the past three years. To obtain
information on genetic testing in Orphanet, it is possible to search by
disease name or by gene (symbol or name in English) in addition to the
traditional search by name of laboratory or professional. The information
provided on laboratories includes data on quality management.
Currently, 1308 laboratories offering tests for 2991 diseases are registered
on the Orphanet database. The test offer differs greatly from
one large country to another: Germany (1940 diseases), France (1630
diseases), Italy (1110 diseases), UK (845 diseases) and Spain (740
diseases). Medium and small-sized countries have a test offer ranging
from 3 to 956 diseases. This situation explains the large cross-border
flow of specimens and underlines the need to organise services at the
European level.
P15.14
Evaluation of four automated mutation detection programs for
clinical re-sequencing.
S. L. Bleoo, R. Tomaszewski, M. Hicks, K. Baptista Wyatt, S. Ordorica, C. L.
Walker, B. Elyas, M. J. Somerville;
University of Alberta, Edmonton, AB, Canada.
Clinical re-sequencing of large genes by capillary electrophoresis requires
software capable of accurate and rapid variant detection. We
identified four commercially available programs, Variant Reporter 1.0
and Seqcape 2.6 (Applied Biosystems), Mutation Surveyor 3.24 (Softgenetics)
and SeqPilot 3.2.1.2 (JSI Medical Systems) and evaluated
their ability to: detect and flag various variants, process large datasets,
utilize HGVS nomenclature, identify regions of interest (ROI) and
de-convolve two alleles. Parameters such as software ease of use,
network performance, audit trail capability and operational costs were
also considered. After preliminary testing, two programs (Seqscape
and Seqpilot) met our minimum diagnostic requirements and were
subjected to a variant analysis of over 2,000,000 bp of bi-directional
sequence (ie. over 4,000,000 bp in total). Both programs had a bi-directional
false-negative rate of 0%, but also have the potential to fail to
alert the user to variants located in a single direction (ie. variants under
primer sequences or miscalls due to incorrect assignment of base
spacing). Additional features important to a diagnostic laboratory such
as electropherogram peak statistics, a mutation database, audit trail
capacity, a client-server application, and the ability to de-convolve heterozygous
indel mutations into two alleles are provided by the SeqPilot
software. Therefore, we have concluded that of the four programs
evaluated, the SeqPilot software provides the greatest overall utility for
clinical re-sequencing of large genes.