2018/04/17 by Stéphanie Tomé, Elodie Dandelot, Céline Dogan +9 · 1 citation
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Genetic Neurodegenerative Diseases #Mitochondrial Function and Pathology #Muscle Physiology and Disorders
paper · doi:10.1002/humu.23531
openalex publication_date 2018/04/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder associated with high variability of symptoms and anticipation. DM1 is caused by an unstable CTG repeat expansion that usually increases in successive generations and tissues. DM1 family pedigrees have shown that ∼90% and 10% of transmissions result in expansions and contractions of the CTG repeat, respectively. To date, the mechanisms of CTG repeat contraction remain poorly documented in DM1. In this report, we identified two new DM1 families with apparent contractions and no worsening of DM1 symptoms in two and three successive maternal transmissions. A new and unique CAG interruption was found in 5' of the CTG expansion in one family, whereas multiple 5' CCG interruptions were detected in the second family. We showed that these interruptions are associated with maternal intergenerational contractions and low somatic mosaicism in blood. By specific triplet-prime PCR, we observed that CTG repeat changes (contractions/expansions) occur preferentially in 3' of the interruptions for both families.