%0 Journal Article
%T IGF2/H19 hypomethylation is tissue, cell, and CpG site dependent and not correlated with body asymmetry in adolescents with Silver-Russell syndrome
%A Kai Kannenberg
%A Karin Weber
%A Cathrin Binder
%A Christina Urban
%A Hans-Joachim Kirschner
%A Gerhard Binder
%J Clinical Epigenetics
%D 2012
%I BioMed Central
%R 10.1186/1868-7083-4-15
%X The ICR1 methylation status was analyzed in blood and in addition in buccal smear probes and cultured fibroblasts obtained from punch biopsies taken from the two body halves of 5 SRS patients and 3 controls. We found that the ICR1 hypomethylation in SRS patients was stronger in blood leukocytes and oral mucosa cells than in fibroblasts. ICR1 CpG sites were affected differently. The severity of hypomethylation was not correlated to body asymmetry. IGF2 expression and IGF-II secretion of fibroblasts were not correlated to the degree of ICR1 hypomethylation. SRS fibroblasts responded well to stimulation by recombinant human IGF-I or IGF-II, with proliferation rates comparable with controls. Clonal expansion of primary fibroblasts confirmed the complexity of the cellular mosaicism.We conclude that the ICR1 hypomethylation SRS is tissue, cell, and CpG site specific. The correlation of the ICR1 hypomethylation to IGF2 and H19 expression is not strict, may depend on the investigated tissue, and may become evident only in case of more severe methylation defects. The body asymmetry in juvenile SRS patients is not related to a corresponding ICR1 hypomethylation gradient, rendering more likely an intrauterine origin of asymmetry. Overall, it may be instrumental to consider not only the ICR1 methylation status as decisive for IGF2/H19 expression regulation.Silver-Russell syndrome (SRS; OMIM 180860) is a sporadically occurring, genetically and clinically heterogeneous disorder. It is diagnosed on the basis of the combination of intrauterine growth retardation, severe short stature, characteristic triangular face, relative macrocephaly, body asymmetry, underweight, and several minor abnormalities [1-3]. The relative limb length differences in asymmetric SRS patients are present at birth and stay stable during the growth process [4]. Short stature in SRS can be treated with pharmacological doses of recombinant growth hormone [5]. There is no apparent hormone deficiency. In contras
%K Silver-Russell syndrome
%K DNA methylation
%K Body asymmetry
%K Skin fibroblast culture
%K IGF-II
%U http://www.clinicalepigeneticsjournal.com/content/4/1/15