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Discrepancies in reporting the CAG repeat lengths for Huntington's disease
- Source :
- European Journal of Human Genetics, Vol. 20, No 1 (2012) pp. 20-6
- Publication Year :
- 2012
-
Abstract
- Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.
- Subjects :
- medicine.medical_specialty
Concordance
International Cooperation
Diagnostic Errors/statistics & numerical data
Nerve Tissue Proteins
Guidelines as Topic
Bioinformatics
Sensitivity and Specificity
Article
Huntingtin Gene
Huntington's disease
Trinucleotide Repeats
Internal medicine
External quality assessment
Genetics
medicine
Humans
Nerve Tissue Proteins/genetics
Diagnostic laboratory
Genetic Testing
Genetic Testing/methods/standards
Allele
Diagnostic Errors
standard reference material
Genetics (clinical)
Alleles
Huntingtin Protein
ddc:618
business.industry
international cooperation
Nuclear Proteins
Reproducibility of Results
Reference Standards
medicine.disease
CAG repeat length
Nuclear Proteins/genetics
Huntington Disease
Huntington Disease/diagnosis
Mutation
Medical genetics
reproducibility of results
mutation
business
Trinucleotide repeat expansion
Huntington Disease/diagnosis/genetics
Genetic Testing/methods
Subjects
Details
- Language :
- English
- ISSN :
- 10184813
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics, Vol. 20, No 1 (2012) pp. 20-6
- Accession number :
- edsair.doi.dedup.....889bb5ecc56cde789666947b81c117e5