Updated Structure of <i>CNBP</i> Repeat Expansions in Patients With Myotonic Dystrophy Type 2 and Its Implication for Standard Diagnostics

Our study revealed the presence of an additional repeat (TCTG)<sub>n</sub> in most of the patients living with DM2. Large expansions of this repeat likely hinder sufficient amplification of the disease causing (CCTG)<sub>n</sub> repeat. Because the (TCTG)<sub>n</sub> repeat is likely mosaic in length, (CCTG)<sub>n</sub> repeat expansions are correctly detected in most patients. However, a few patients are at risk of a false-negative result using the standard RP-PCR, which had a false-negative rate of 0.7% (5/674) and a sensitivity of 97.3% in the cohort studied. Based on our findings, we propose (TG)<sub>v</sub>(TCTG)<sub>w</sub>(CCTG)<sub>n</sub>(TCTG')<sub>m</sub> as the updated model for the structure of <i>CNBP</i> repeat expansions and recommend adapting the diagnostic guidelines accordingly. The effect of the (TCTG)<sub>n</sub> repeat on the phenotype remains to be determined but could be key for establishing a phenotype-genotype correlation for DM2 that remained elusive so far.

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Publication Details

Journal
Neurology Genetics
Published
2024-12-18
DOI
https://doi.org/10.1212/nxg.0000000000200220
Primary Topic
Genetic Neurodegenerative Diseases
Type
article
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article

Updated Structure of CNBP Repeat Expansions in Patients With Myotonic Dystrophy Type 2 and Its Implication for Standard Diagnostics

Stephan Wenninger, Gilbert Wunderlich, Maggie Christine Walter, Teresa Neuhann et al.
Neurology Genetics
Genetic Neurodegenerative Diseases
article

Updated Structure of CNBP Repeat Expansions in Patients With Myotonic Dystrophy Type 2 and Its Implication for Standard Diagnostics

Stephan Wenninger, Gilbert Wunderlich, Maggie Christine Walter, Teresa Neuhann, Martin Wendlandt, Kerstin Becker, Benedikt G. H. Schoser, Hannes Erdmann, Elke Holinski‐Feder, Stephanie Kleinle, Morghan C. Lucas, Angela Abicht, Andrea Bier, Simone Rost, Manuela Timmer
article en

Abstract

Our study revealed the presence of an additional repeat (TCTG)<sub>n</sub> in most of the patients living with DM2. Large expansions of this repeat likely hinder sufficient amplification of the disease causing (CCTG)<sub>n</sub> repeat. Because the (TCTG)<sub>n</sub> repeat is likely mosaic in length, (CCTG)<sub>n</sub> repeat expansions are correctly detected in most patients. However, a few patients are at risk of a false-negative result using the standard RP-PCR, which had a false-negative rate of 0.7% (5/674) and a sensitivity of 97.3% in the cohort studied. Based on our findings, we propose (TG)<sub>v</sub>(TCTG)<sub>w</sub>(CCTG)<sub>n</sub>(TCTG')<sub>m</sub> as the updated model for the structure of <i>CNBP</i> repeat expansions and recommend adapting the diagnostic guidelines accordingly. The effect of the (TCTG)<sub>n</sub> repeat on the phenotype remains to be determined but could be key for establishing a phenotype-genotype correlation for DM2 that remained elusive so far.

Neurology GeneticsVol. 11(1)
University of Würzburg (DE), Universitätsmedizin Greifswald (DE), LMU Klinikum (DE), Medical Genetics Center (DE), Friedrich Baur Stiftung (DE), Praxis für Humangenetik (DE), University Hospital Cologne (DE), Ludwig-Maximilians-Universität München (DE)
Openalex Percentile: Top 75%
Genetic Neurodegenerative Diseases
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