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Methylation pattern of the GRB10 and MEST genes and the 11p15 region in patients with Silver-Russell syndrome

Grant number: 07/02628-6
Support type:Scholarships in Brazil - Master
Effective date (Start): April 01, 2008
Effective date (End): March 31, 2009
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Ester Silveira Ramos
Grantee:Jaqueline Carvalho de Oliveira
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


The main feature of Silver-Russell syndrome (SRS) is pre- and postnatal growth restriction. The disorder is clinically and genetically heterogeneous and recently the involvement of genomic imprinting in the etiology was suggested. A major subset of imprinted genes is involved in fetal growth, among them some genes in the 11p15 region. In this region the IGF2 gene encodes the insulin-like growth factor II, one of the main fetal growth factors. IGF2 is paternally expressed and it is regulated by a ICR (imprinting control region) named H19DMR. The CDKN1C gene, acting negatively to regulate cell proliferation, is also mapped in the 11p15 region and it is regulated by the ICR KvDMR1 maternal methylated and with paternal expression. Recent studies provide evidence for a role of IGF2 in SRS etiology. They reported patients who had hypomethylation of the H19DMR in high frequency (31-50%) and, in 2007, evidence for a role of KvDMR1 was also suggested. However, the true relationship of the epigenetics alterations and the SRS remain uncertain. From these data, the aim of our study is analyze the presence of parental disomy and the methylation status of the 11p15 region by molecular techniques (PCR, RFLP, Real Time PCR) in patients with SSR. The results will be used to analyze the incidence of alteration in these ICRs in patients with SRS and to verify the use of this methodology for diagnostic test in clinical routine. (AU)