Complex Tissue-Specific Epigenotypes in Russell-Silver Syndrome Associated with 11p15 ICR1 Hypomethylation

Salah Azzi, Annick Blaise, Virginie Steunou, Madeleine D. Harbison, Jennifer Salem, Frédéric Brioude, Sylvie Rossignol, Walid Abi Habib, Nathalie Thibaud, Cristina Das Neves, Marilyne Le Jule, Cécile Brachet, Claudine Heinrichs, Yves Le Bouc, Irène Netchine

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Russell-Silver Syndrome (RSS) is a prenatal and postnatal growth retardation syndrome caused mainly by 11p15 ICR1 hypomethylation. Clinical presentation is heterogeneous in RSS patients with 11p15 ICR1 hypomethylation. We previously identified a subset of RSS patients with 11p15 ICR1 and multilocus hypomethylation. Here, we examine the relationships between IGF2 expression, 11p15 ICR1 methylation, and multilocus imprinting defects in various cell types from 39 RSS patients with 11p15 ICR1 hypomethylation in leukocyte DNA. 11p15 ICR1 hypomethylation was more pronounced in leukocytes than in buccal mucosa cells. Skin fibroblast IGF2 expression was correlated with the degree of ICR1 hypomethylation. Different tissue-specific multilocus methylation defects coexisted in 38% of cases, with some loci hypomethylated and others hypermethylated within the same cell type in some cases. Our new results suggest that tissue-specific epigenotypes may lead to clinical heterogeneity in RSS.

Original languageEnglish
Pages (from-to)1211-1220
Number of pages10
JournalHuman Mutation
Issue number10
StatePublished - 1 Oct 2014


  • 11p15 region
  • Fetal and postnatal development
  • Mutlilocus imprinting disorders
  • Russell-Silver Syndrome


Dive into the research topics of 'Complex Tissue-Specific Epigenotypes in Russell-Silver Syndrome Associated with 11p15 ICR1 Hypomethylation'. Together they form a unique fingerprint.

Cite this