Population-Based Prevalence of Myotonic Dystrophy Type 1 Using Genetic Analysis of Statewide Blood Screening Program
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- 16 February 2021
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 96 (7), e1045-e1053
- https://doi.org/10.1212/wnl.0000000000011425
Abstract
Objective To determine whether the genetic prevalence of the CTG expansion in the DMPK gene associated with myotonic dystrophy type 1 (DM1) in an unbiased cohort is higher than previously reported population estimates, ranging from 5 to 20 per 100,000 individuals. Methods This study used a cross-sectional cohort of deidentified dried blood spots from the newborn screening program in the state of New York, taken from consecutive births from 2013 to 2014. Blood spots were screened for the CTG repeat expansion in the DMPK gene using triplet-repeat primed PCR and melt curve analysis. Melt curve morphology was assessed by 4 blinded reviewers to identify samples with possible CTG expansion. Expansion of the CTG repeat was validated by PCR fragment sizing using capillary electrophoresis for samples classified as positive or premutation to confirm the result. Prevalence was calculated as the number of samples with CTG repeat size ≥50 repeats compared to the overall cohort. Results Of 50,382 consecutive births, there were 24 with a CTG repeat expansion ≥50, consistent with a diagnosis of DM1. This represents a significantly higher DM1 prevalence of 4.76 per 10,000 births (95% confidence interval 2.86–6.67) or 1 in every 2,100 births. There were an additional 96 samples (19.1 per 10,000 or 1 in 525 births) with a CTG expansion in the DMPK gene in the premutation range (CTG)35–49. Conclusion The prevalence of individuals with CTG repeat expansions in DMPK is up to 5 times higher than previous reported estimates. This suggests that DM1, with multisystemic manifestations, is likely underdiagnosed in practice.Keywords
This publication has 22 references indexed in Scilit:
- Myotonic Dystrophy: From Bench to BedsideSeminars in Neurology, 2012
- Robust relationship inference in genome-wide association studiesBioinformatics, 2010
- Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic populationBrain, 2009
- Fast model-based estimation of ancestry in unrelated individualsGenome Research, 2009
- Simple Procedure for Automatic Detection of Unstable Alleles in the Myotonic Dystrophy and Huntington's Disease LociGenetic Testing, 2006
- A Global Haplotype Analysis of the Myotonic Dystrophy Locus: Implications for the Evolution of Modern Humans and for the Origin of Myotonic Dystrophy MutationsAmerican Journal of Human Genetics, 1998
- Origin of the expansion mutation in myotonic dystrophyNature Genetics, 1993
- An Unstable Triplet Repeat in a Gene Related to Myotonic Muscular DystrophyScience, 1992
- Myotonic Dystrophy Mutation: an Unstable CTG Repeat in the 3′ Untranslated region of the GeneScience, 1992
- Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family memberCell, 1992