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

doi:10.1002/humu.22623

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

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34 Scopus citations

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.

Original language	English
Pages (from-to)	1211-1220
Number of pages	10
Journal	Human Mutation
Volume	35
Issue number	10
DOIs	https://doi.org/10.1002/humu.22623
State	Published - 1 Oct 2014

Keywords

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

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10.1002/humu.22623

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Azzi, S., Blaise, A., Steunou, V., Harbison, M. D., Salem, J., Brioude, F., Rossignol, S., Habib, W. A., Thibaud, N., Neves, C. D., Jule, M. L., Brachet, C., Heinrichs, C., Bouc, Y. L., & Netchine, I. (2014). Complex Tissue-Specific Epigenotypes in Russell-Silver Syndrome Associated with 11p15 ICR1 Hypomethylation. Human Mutation, 35(10), 1211-1220. https://doi.org/10.1002/humu.22623

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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.",

keywords = "11p15 region, Fetal and postnatal development, Mutlilocus imprinting disorders, Russell-Silver Syndrome",

author = "Salah Azzi and Annick Blaise and Virginie Steunou and Harbison, {Madeleine D.} and Jennifer Salem and Fr{\'e}d{\'e}ric Brioude and Sylvie Rossignol and Habib, {Walid Abi} and Nathalie Thibaud and Neves, {Cristina Das} and Jule, {Marilyne Le} and C{\'e}cile Brachet and Claudine Heinrichs and Bouc, {Yves Le} and Ir{\`e}ne Netchine",

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Azzi, S, Blaise, A, Steunou, V, Harbison, MD, Salem, J, Brioude, F, Rossignol, S, Habib, WA, Thibaud, N, Neves, CD, Jule, ML, Brachet, C, Heinrichs, C, Bouc, YL & Netchine, I 2014, 'Complex Tissue-Specific Epigenotypes in Russell-Silver Syndrome Associated with 11p15 ICR1 Hypomethylation', Human Mutation, vol. 35, no. 10, pp. 1211-1220. https://doi.org/10.1002/humu.22623

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T1 - Complex Tissue-Specific Epigenotypes in Russell-Silver Syndrome Associated with 11p15 ICR1 Hypomethylation

AU - Azzi, Salah

AU - Blaise, Annick

AU - Steunou, Virginie

AU - Harbison, Madeleine D.

AU - Salem, Jennifer

AU - Brioude, Frédéric

AU - Rossignol, Sylvie

AU - Habib, Walid Abi

AU - Thibaud, Nathalie

AU - Neves, Cristina Das

AU - Jule, Marilyne Le

AU - Brachet, Cécile

AU - Heinrichs, Claudine

AU - Bouc, Yves Le

AU - Netchine, Irène

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

KW - 11p15 region

KW - Fetal and postnatal development

KW - Mutlilocus imprinting disorders

KW - Russell-Silver Syndrome

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SP - 1211

EP - 1220

JO - Human Mutation

JF - Human Mutation

IS - 10

ER -

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

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