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Practice Guideline
. 2024 Aug;26(8):101145.
doi: 10.1016/j.gim.2024.101145. Epub 2024 Jun 5.

Myotonic dystrophy type 1 testing, 2024 revision: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

Bryce A Seifert  1 , Honey V Reddi  2 , Benjamin E Kang  3 , Lora J H Bean  4 , Amy Shealy  5 , Nancy C Rose  6 ; ACMG Laboratory Quality Assurance Committee. Electronic address: documents@acmg.net  7
Affiliations
Practice Guideline

Myotonic dystrophy type 1 testing, 2024 revision: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

Bryce A Seifert et al. Genet Med. 2024 Aug.

Abstract

Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy causing progressive muscle loss and weakness. Although clinical features can manifest at any age, it is the most common form of muscular dystrophy with onset in adulthood. DM1 is an autosomal dominant condition, resulting from an unstable CTG expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. The age of onset and the severity of the phenotype are roughly correlated with the size of the CTG expansion. Multiple methodologies can be used to diagnose affected individuals with DM1, including polymerase chain reaction, Southern blot, and triplet repeat-primed polymerase chain reaction. Recently, triplet repeat interruptions have been described, which may affect clinical outcomes of a fully-variable allele in DMPK. This document supersedes the Technical Standards and Guidelines for Myotonic Dystrophy originally published in 2009 and reaffirmed in 2015. It is designed for genetic testing professionals who are already familiar with the disease and the methods of analysis.

Keywords: Myotonic dystrophy; Technical standard; Testing methodologies; Trinucleotide repeats.

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Conflict of interest statement

Conflict of Interest Honey V. Reddi, Benjamin E. Kang, and Lora J.H. Bean all serve as directors in clinical laboratories that perform a breadth of genetic and genomic analyses on a fee-for-service basis. Honey V. Reddi is a Consultant Director for Biofidelity Inc. Bryce A. Seifert is a salaried employee of Guidehouse, LLP. All other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.. Diagnostic testing algorithm for myotonic dystrophy type 1.
Ranges of DMPK CTG repeats are as follows: normal alleles (~5 to 34 CTG repeats), variable alleles (~35 to 49 CTG repeats), fully-variable alleles (50 or more CTG repeats). PCR, polymerase chain reaction; TP-PCR, triplet repeat-primed PCR.
Figure 2.
Figure 2.. Southern blot detection of the CTG expansion in DMPK.
HindIII-BglI digested genomic DNA probed with pMDY1. Samples in Lanes 1 and 8 are unaffected controls. Samples from patients with DM1 (Lanes 2–7) show an expanded fragment representing a DM1 allele. The normal allele is 2.2 kb.
Figure 3.
Figure 3.. Triplet repeat-primed PCR results.
A. Individual with 12 and 15 CTG repeats in DMPK. CTG repeat sizes are indicated above each peak. B. Individual that is homozygous for 10 CTG repeats. The inset depicts the absence of a stutter pattern. C. Individual with 12 CTG repeats and a fully-variable allele in DMPK (50 or more CTG repeats). The inset depicts a stutter pattern, consistent with a fully-variable allele (50 or more CTG repeats) in DMPK.
See this image and copyright information in PMC

References

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