TY - JOUR
T1 - Results from an external proficiency testing program
T2 - 11 years of molecular genetics testing for myotonic dystrophy type 1
AU - Richards, C. Sue
AU - Palomaki, Glenn E.
AU - Hegde, Madhuri
N1 - Publisher Copyright:
© 2016 American College of Medical Genetics and Genomics.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - External proficiency testing
KW - myotonic dystrophy type 1
KW - trinucleotide repeats
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U2 - 10.1038/gim.2016.59
DO - 10.1038/gim.2016.59
M3 - Article
C2 - 27253733
AN - SCOPUS:85000443609
SN - 1098-3600
VL - 18
SP - 1290
EP - 1294
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 12
ER -