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The European Molecular Genetics Quality Network (EMQN) has been organizing an external quality assessment (EQA) scheme for molecular genetic testing of trinucleotide repeat mutations in the spinocerebellar ataxias (SCAs) since 2004. DNA samples were validated by at least two independent labs and two different methods. Together with mock clinical case descriptions and requests for specific SCA gene analyses, these were sent to registered participants each year. Laboratories were asked to use their routine procedures and protocols. A panel of assessors reviewed the final returns, including genotype results and reports, to assess the quality of (1) genotyping and (2) interpretation and reporting. A description of methods and raw data were also requested and were very useful for the final analysis. Altogether, during 3 years, 239 reports were received from the laboratories. Overall genotype error rate ranged 1.1-5.2%, a significant cause of concern. Scores for interpretation and reporting also showed that there is still much room for progress, although performance has improved over this period of assessment. The consequences of suboptimal laboratory practices, genotyping errors and misdiagnosis and of incorrect or incomplete interpretation and reporting have wide implications for patient lives, as well as for health management and counselling of relatives. EQA schemes are an important part of quality assurance in molecular genetic laboratories, and their use should become a routine part of laboratory diagnostic practice. Current evidence shows also that it is important that laboratories participate on a yearly basis and that this becomes mandatory for reference laboratories.

Objective: To compare data on the practices of molecular genetic testing (MGT) in laboratories in the United States with those in 18 other countries., Methods: A Web-based survey of MGT laboratory directors (n = 827; response rate 63%) in 18 countries on three continents was carried out, and the response from U.S. laboratories compared to all others. Quality assurance and reporting indices were developed and calculated for each responding laboratory., Results: A comparison of U.S. results with all other countries identified differences in laboratory setting, personnel qualifications, and the specific tests being offered, but similar rates of adherence to MGT quality standards and reporting practices were found. The survey also documented substantial transborder flow of specimens, most commonly due to the lack of availability of the test in the United States or because the test was available only through a research protocol, highlighting the need for common reporting and practice guidelines for the international MGT community., Conclusion: The findings presented here provide further support for the need to consider the application of the Organisation for Economic Cooperation and Development (OECD) Guidelines and the establishment of compatible accreditation programs or equivalent mechanisms across national borders to ensure the quality of laboratory services and the clinical usefulness of molecular genetic test reports for referred specimens.

Background: In the past 15 years, clinical laboratory science has been transformed by the use of technologies that cross the traditional boundaries between laboratory disciplines. However, during this period, issues of quality have not always been given adequate attention. The European Molecular Genetics Quality Network (EMQN) has developed a novel external quality assessment scheme for evaluation of DNA sequencing. We report the results of an international survey of the quality of DNA sequencing among 64 laboratories from 21 countries., Methods: Current practice for DNA sequence analysis was established by use of an online questionnaire. Participating laboratories were provided with 4 DNA samples of validated genotype. Evaluation of the results included assessing the quality of sequence data, variant genotypes, and mutation nomenclature. To accommodate variations in mutation nomenclature, variants indicated by participants were scored for compliance with 3 acceptable marking schemes., Results: A total of 346 genotypes were analyzed. Of these, 19 (5%) genotyping errors were made. Of these, 10 (53%) were false-negative and 9 (47%) were false-positive results. A further 27 (8%) errors were made in naming mutations. Results were analyzed for 3 indicators of data quality: PHRED quality scores, Quality Read Length, and Quality Read Overlap. Most laboratories produced results of acceptable diagnostic quality as judged by these indicators. The results were used to calculate a consensus benchmark for DNA sequencing against which individual laboratories could rank their performance., Conclusions: We propose that the consensus benchmark can be used as a baseline against which the aggregate and individual laboratory standard of DNA sequencing may be tracked from year to year.

This paper reports a European pilot External Quality Assessment (EQA) scheme for the molecular diagnosis of Huntington's disease (HD). The European Molecular Genetics Quality Network (EMQN) chose HD as a relatively simple assay that allows a range of difficulty in terms of technical competence and interpretation. Fourteen centres from 12 different countries participated. The scheme organiser provided five cases together with mock clinical information. The participating laboratories were asked to complete the analyses and return the reports in English to their normal laboratory format within a fixed period. The scheme demonstrates a level of potential misdiagnosis in molecular analysis of HD as well as a wide variety in way of reporting laboratory results. Overall 9/146 (6.2%) of alleles fell outside the set limits, and the rate of misdiagnosis was 1/78 (1.3%). A closer estimate of diagnostic accuracy will require expansion of the scheme.