Results from an external proficiency testing program: 11 years of molecular genetics testing for myotonic dystrophy type 1.

PURPOSE

The aim of this study was to examine the performance of laboratories offering assessment for myotonic dystrophy type 1 (DM1) using external proficiency testing samples. DM1, a dominant disorder, has a prevalence of 1:20,000 due to the expansion of CTG trinucleotide repeats in the DMPK gene.

METHODS

External proficiency testing administered by the College of American Pathologists/American College of Medical Genetics and Genomics distributes three samples twice yearly. Responses from 2003 through the first distribution of 2013 were analyzed after stratification by location (United States/international). Both the repeat sizes (analytic validity) and clinical interpretations were assessed.

RESULTS

Over the 21 distributions, 45 US and 29 international laboratories participated. Analytic sensitivity for detecting and reporting expanded repeats (≥50) was 99.2% (382/385 challenges) and 97.1% (133/137 challenges), respectively. Analytic specificity (to within two repeats of the consensus) was 99.2% (1,790/1,805 alleles) and 98.6% (702/712 alleles), respectively. Clinical interpretations were correct for 99.3% (450/453) and 98.2% (224/228) of positive challenges and in 99.9% (936/937) and 99.6% (455/457) of negative challenges, respectively. Of four incorrect interpretations made in the United States, two were probably due to sample mix-up.

CONCLUSION

This review of laboratory performance regarding laboratory-developed genetic tests indicates very high performance for both the analytic and interpretative challenges for DM1.Genet Med 18 12, 1290-1294.