External Quality Assessment in Molecular Genetic Testing

SummaryMolecular genetic analysis of families with haemophilia and other inherited bleeding disorders is nowa common laboratory investigation. In contrast to phenotypic testing in which strict quality control is adhered to, in haemophilia molecular genetic testing there has been a lack of any external quality assurance schemes. In 1998 the UK National External Quality Assessment Scheme (UK NEQAS) established a pilot quality assurance scheme for molecular genetic testing in haemophilia. Results from three initial surveys highlighted problems with the quality of samples when used to screen for the intron 22 inversion within the F8 gene. The scheme was re-launched in 2003, and since that time there have been five exercises involving whole blood or immortalised cell line DNA. The results together with an overall summary of the exercise are subsequently returned to participants. Exercises to date have focused exclusively on haemophilia A and QA, material has included screening for the intron 1 and intron 22 inversions as well as sequence analysis. A paper exercise circulated in 2003 highlighted problems with the format of reports and, following feedback to participants, onlya single error has been made in the subsequent four exercises. Participating laboratories now receive QA material every six months. Immortalised cell line material was introduced in 2005 and was shown to perform well. This will allow expansion of the scheme and a reduction in the dependence on blood donation.

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THE UK NATIONAL EXTERNAL QUALITY ASSESSMENT SCHEME (UK NEQAS) FOR MOLECULAR GENETIC TESTING IN HAEMOPHILIA

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2007.tb01883.x ◽

2007 ◽

Vol 5 ◽

pp. P-T-125-P-T-125

Author(s):

D.J. Perry ◽

A. Goodeve ◽

M. Hill ◽

I. Jennings ◽

S. Kitchen ◽

...

Keyword(s):

Genetic Testing ◽

Quality Assessment ◽

External Quality Assessment ◽

Molecular Genetic ◽

Molecular Genetic Testing ◽

External Quality ◽

External Quality Assessment Scheme ◽

The Uk

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Thirteen Years of an International External Quality Assessment Scheme for Genotyping: Results and Recommendations

Clinical Chemistry ◽

10.1373/clinchem.2016.254482 ◽

2016 ◽

Vol 62 (8) ◽

pp. 1084-1095 ◽

Cited By ~ 10

Author(s):

Verena Haselmann ◽

Wolf J Geilenkeuser ◽

Simona Helfert ◽

Romy Eichner ◽

Svetlana Hetjens ◽

...

Keyword(s):

Genetic Testing ◽

Quality Assessment ◽

Error Rate ◽

External Quality Assessment ◽

Molecular Genetic ◽

Genetic Diagnostics ◽

External Quality ◽

Sequence Variations ◽

Therapeutic Decisions

Abstract BACKGROUND Suboptimal laboratory procedures resulting in genotyping errors, misdiagnosis, or incorrect reporting bear greatly on a patient's health management, therapeutic decisions made on their behalf, and ultimate outcome. Participation in external quality assessment (EQA) is a key element of quality assurance in molecular genetic diagnostics. Therefore, the Reference Institute for Bioanalytics has tried for 13 years to improve the quality of genetic testing by offering an EQA for different clinically relevant sequence variations. METHODS Within each of the biannual EQA schemes offered, up to 18 samples of lyophilized human genomic DNA were provided for up to 50 different molecular genetic tests. Laboratories were asked to use their routine procedures for genotyping. At least 2 expert peer assessors reviewed the final returns. Data from 2002 to 2014 were evaluated. RESULTS In total, 82 462 reported results from 812 characterized samples were evaluated. Globally, the number of participants increased each year along with the number of sequence variations offered. The error rate decreased significantly over the years with an overall error rate of 1.44%. Additionally, a decreased error rate for samples repeated over time was noted. Interestingly, the error rate showed a high difference depending on the locus analyzed and the method used. CONCLUSIONS Based on the evaluation of this long-term EQA scheme, various recommendations can be given to improve the quality of molecular genetic testing, such as the use of 2 different methods for genotyping. Furthermore, some methods are inappropriate for analysis of certain sequence variations.

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The Italian National External Quality Assessment Program in Molecular Genetic Testing: Results of the VII Round (2010-2011)

BioMed Research International ◽

10.1155/2013/739010 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

F. Censi ◽

F. Tosto ◽

G. Floridia ◽

M. Marra ◽

M. Salvatore ◽

...

Keyword(s):

Genetic Testing ◽

External Quality Assessment ◽

Fragile X ◽

Molecular Genetic ◽

Beta Thalassemia ◽

Molecular Genetic Testing ◽

Quality Assurance Programme ◽

Familial Adenomatous Polyposis Coli ◽

Public And Private ◽

Routine Procedures

Since 2001 the Istituto Superiore di Sanità established a quality assurance programme for molecular genetic testing that covers four pathologies: Cystic Fibrosis (CF), Beta Thalassemia (BT), Fragile X Syndrome (FX), and Familial Adenomatous Polyposis Coli (APC). Since 2009 this activity is an institutional activity and participation is open to both public and private laboratories. Seven rounds have been performed until now and the eighth is in progress. Laboratories receive 4 DNA samples with mock clinical indications. They analyze the samples using their routine procedures. A panel of assessors review the raw data and the reports; all data are managed through a web utility. In 2010 the number of participants was 43, 17, 15, 5 for CF, BT, FX, APC schemes respectively. Genotyping results were correct in 96%, 98.5%, 100%, and 100% of CF, BT, FX, and APC samples, respectively. Interpretation was correct in 74%, 91%, 88%, and 60% of CF, BT, FX, and APC reports, respectively; however in most of them it was not complete but a referral to genetic counseling was given. Reports were satisfactory in more than 60% of samples in all schemes. This work presents the 2010 results in detail comparing our data with those from other European schemes.

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Quality assessment in cytogenetic and molecular genetic testing: the experience of the Italian Project on Standardisation and Quality Assurance

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2004.148 ◽

2004 ◽

Vol 42 (8) ◽

Cited By ~ 19

Author(s):

Domenica Taruscio ◽

Vincenzo Falbo ◽

Giovanna Floridia ◽

Marco Salvatore ◽

Chiara Pescucci ◽

...

Keyword(s):

Cystic Fibrosis ◽

Quality Assessment ◽

External Quality Assessment ◽

Fragile X ◽

Molecular Genetic ◽

Adenomatous Polyposis ◽

Polyposis Coli ◽

External Quality ◽

Familial Adenomatous Polyposis Coli ◽

Analytical Accuracy

AbstractThe first Italian national trial of external quality assessment in genetic testing was organised within the framework of the “Italian National Project for Standardisation and Quality Assurance of Genetic Tests”. Sixty-eight Public Health Service laboratories volunteered for the trial, which involved molecular genetic tests (cystic fibrosis, β-thalassaemia, familial adenomatous polyposis coli and fragile-X syndrome) and cytogenetic tests (prenatal and postnatal, the latter included cancer cytogenetics). The response rate was high (88.2%). The level of analytical accuracy was good, i.e., the percentage of laboratories that correctly genotyped all samples was 89.3% for cystic fibrosis, 90.9% for β-thalassaemia, 100% for familial adenomatous polyposis coli (despite two laboratories did not complete the analysis because the amount of DNA was considered insufficient), and 90.5% for fragile-X syndrome. Written reports differed widely and were judged “inadequate” in over 50% of cases. Most laboratories from the present study already have experience in previous European external quality assessments for at least one genetic test; this can explain the higher analytical accuracy in the Italian external quality assessment with respect to quality control programmes in other countries. Collaborative networks are strongly suggested to improve the quality of the reports.

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