Germline correction of an epimutation related to Silver-Russell syndrome.

Abstract

Like genetic mutations, DNA methylation anomalies or epimutations can disrupt gene expression and lead to human diseases. However, unlike genetic mutations, epimutations can in theory be reverted through developmental epigenetic reprograming, which should limit their transmission across generations. Following the request for a parental project of a patient diagnosed with Silver-Russell syndrome (SRS), and the availability of both somatic and spermatozoa DNA from the proband and his father, we had the exceptional opportunity to evaluate the question of inheritance of an epimutation. We provide here for the first time evidence for efficient reversion of a constitutive epimutation in the spermatozoa of an SRS patient, which has important implication for genetic counseling.

• Authors: Céline Bruno, Virginie Carmignac, Irène Netchine, Cécile Choux, Yannis Duffourd, Laurence Faivre, Christel Thauvin-Robinet, Yves Le Bouc, Paul Sagot, Déborah Bourc'his, Patricia Fauque
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 24 Issue 12 Pg. 3314-21 (Jun 15 2015) ISSN: 1460-2083 [Electronic] England
• PMID: 25736213 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• H19 long non-coding RNA
• RNA, Long Noncoding

Topics

• Adult
• CpG Islands
• DNA Methylation
• Epigenesis, Genetic
• Exome
• Female
• Gene Expression Regulation
• Gene Order
• Genetic Loci
• Genomic Imprinting
• Germ Cells (metabolism)
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Phenotype
• Promoter Regions, Genetic
• RNA, Long Noncoding (genetics)
• Silver-Russell Syndrome (diagnosis, genetics)