C Sue Richards1, Glenn E Palomaki2, Madhuri Hegde3. 1. Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, USA. 2. Department of Pathology and Laboratory Medicine, Women & Infants Hospital and the Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. 3. Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Abstract
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.
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.
Authors: Georgia Besant; Pierre R Bourque; Ian C Smith; Sharon Chih; Mariana M Lamacie; Ari Breiner; Jocelyn Zwicker; Hanns Lochmüller; Jodi Warman-Chardon Journal: Front Cardiovasc Med Date: 2022-06-03
Authors: Devin Oglesbee; Tina M Cowan; Marzia Pasquali; Timothy C Wood; Karen E Weck; Thomas Long; Glenn E Palomaki Journal: Genet Med Date: 2017-06-29 Impact factor: 8.822