title: Complex tissue-specific epigenotypes in Russell-Silver Syndrome associated with 11p15 ICR1 hypomethylation.
abstract: 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.
authors.affiliation: INSERM, UMR_S 938, CDR Saint-Antoine, Paris, F-75012, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, Paris, F-75012, France; APHP, Armand Trousseau Hospital, Pediatric Endocrinology, Paris, France.
authors.forename: Salah
authors.initials: S
authors.lastname: Azzi
authors.forename: Annick
authors.initials: A
authors.lastname: Blaise
authors.forename: Virginie
authors.initials: V
authors.lastname: Steunou
authors.forename: Madeleine D
authors.initials: MD
authors.lastname: Harbison
authors.forename: Jennifer
authors.initials: J
authors.lastname: Salem
authors.forename: Frédéric
authors.initials: F
authors.lastname: Brioude
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rossignol
authors.forename: Walid Abi
authors.initials: WA
authors.lastname: Habib
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thibaud
authors.forename: Cristina Das
authors.initials: CD
authors.lastname: Neves
authors.forename: Marilyne Le
authors.initials: ML
authors.lastname: Jule
authors.forename: Cécile
authors.initials: C
authors.lastname: Brachet
authors.forename: Claudine
authors.initials: C
authors.lastname: Heinrichs
authors.forename: Yves Le
authors.initials: YL
authors.lastname: Bouc
authors.forename: Irène
authors.initials: I
authors.lastname: Netchine
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019175:DNA Methylation; D004848:Epithelium / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D009061:Mouth Mucosa / Q000378:metabolism; D009928:Organ Specificity; D056730:Silver-Russell Syndrome / Q000235:genetics*; D012867:Skin / Q000378:metabolism
chemical_list: D007335:Insulin-Like Growth Factor II
keywords: 11p15 region; Russell-Silver Syndrome; fetal and postnatal development; mutlilocus imprinting disorders