Myotonic dystrophy type 1 (DM1) is an autosomal dominant, multisystemic disorder due to an unstable expansion of CTG repetition in the 3′ UTR of the DMPK gene, which increases in length during gametogenesis, causing genetic anticipation. Nevertheless, contraction of the DM1 expanded alleles has been reported in 10% of paternal and at 3% of maternal transmissions, mostly associated with less severe symptoms and a later age of onset. The aim of this study is to investigate the inheritance and meiotic instability of a paternal DMPK expanded allele that contracted into the normal range in an asymptomatic member of a DM1 family. We genetically characterized the DMPK gene in a DM1 family through a combination of SR-PCR, TP-PCR, LR-PCR and linkage analysis. We described a DM1 family with an asymptomatic 40-year-old woman inheriting from the affected father the DMPK repeat contracted in size to a (CTG)30 allele. In prenatal diagnosis requested from the woman, we observed two DMPK alleles within the normal range in foetal DNA, one of them corresponding to the contracted maternal allele, which remained stable in the intergenerational transmission. We demonstrated, for the first time, that a reverted DMPK allele remains stable through maternal meiotic transmission, thus implementing our knowledge about the intergenerational dynamics of the DM1 locus.
- Open Access
- Article
Identification of a Reverted DMPK Allele and Analysis of Intergenerational Transmission in a DM1 Pedigree
- Virginia Veronica Visconti 1,
- Paola Bisceglia 2,
- Angela De Dominicis 3,
- Elena Pegoraro 4,
- Corrado Angelini 4,
- Federica Sangiuolo 1,
- Annalisa Botta 1,
- Maria Rosaria D'Apice 5,
- Giuseppe Novelli 1, 5, *
Author Information
Received: 01 Aug 2025 | Revised: 05 Sep 2025 | Accepted: 15 Sep 2025 | Published: 03 Dec 2025
Abstract
Keywords
myotonic dystrophy type 1 (DM1) | CTG repeat | DMPK gene | repeat contractions | meiotic transmission
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