1. DMPK hypermethylation in sperm cells of myotonic dystrophy type 1 patients
- Author
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Pauline Megalli, Talia Eldar-Geva, Rachel Eiges, Silvina Epsztejn-Litman, Gheona Altarescu, Oshrat Schonberger, Shira Yanovsky-Dagan, Eliora Cohen, The Hebrew University Hadassah Medical School, Shaare Zedek Medical Center [Jerusalem, Israel], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Centre de Recherche en Myologie, and Association Institut de Myologie [Paris]
- Subjects
musculoskeletal diseases ,Male ,Untranslated region ,Somatic cell ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Biology ,Myotonic dystrophy ,Myotonin-Protein Kinase ,Germline ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Semen ,Genetics ,medicine ,Humans ,Myotonic Dystrophy ,Muscular dystrophy ,Gene ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,DNA Methylation ,medicine.disease ,Spermatozoa ,Sperm ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,DNA methylation ,Trinucleotide Repeat Expansion ,030217 neurology & neurosurgery - Abstract
Myotonic dystrophy type 1 (DM1) is an autosomal dominant muscular dystrophy that results from a CTG expansion (50–4000 copies) in the 3′ UTR of the DMPK gene. The disease is classified into four or five somewhat overlapping forms, which incompletely correlate with expansion size in somatic cells of patients. With rare exception, it is affected mothers who transmit the congenital (CDM1) and most severe form of the disease. Why CDM1 is hardly ever transmitted by fathers remains unknown. One model to explain the almost exclusive transmission of CDM1 by affected mothers suggests a selection against hypermethylated large expansions in the germline of male patients. By assessing DNA methylation upstream to the CTG expansion in motile sperm cells of four DM1 patients, together with availability of human embryonic stem cell (hESCs) lines with paternally inherited hypermethylated expansions, we exclude the possibility that DMPK hypermethylation leads to selection against viable sperm cells (as indicated by motility) in DM1 patients.
- Published
- 2021
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