no evidence for mutations of ctcflboris in silver-russell syndrome patients with igf2h19 imprinting control region 1 hypomethylation没有证据表明ctcflboris突变的silver-russell综合症患者1 hypomethylation igf2h19印迹控制区域.pdfVIP

No Evidence for Mutations of CTCFL/BORIS in Silver- Russell Syndrome Patients with IGF2/H19 Imprinting Control Region 1 Hypomethylation 1 2 1 Jeremiah Bernier-Latmani , Alessandra Baumer , Phillip Shaw * ¨ 1 Experimental Pathology Division, Institute of Pathology, University of Lausanne, Lausanne, Switzerland, 2 Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland Abstract Background: Silver-Russell syndrome (SRS) is a genetically and clinically heterogeneous disease. Although no protein coding gene defects have been reported in SRS patients, approximately 50% of SRS patients carry epimutations (hypomethylation) at the IGF2/H19 imprinting control region 1 (ICR1). Proper methylation at ICR1 is crucial for the imprinted expression of IGF2, a fetal growth factor. CTCFL, a testis-specific protein, has recently been proposed to play a role in the establishment of DNA methylation at the murine equivalent of ICR1. A screen was undertaken to assess whether CTCFL is mutated in SRS patients with hypomethylation, to explore a link between the observed epimutations and a genetic cause of the disease. Methodology/Principal Findings: DNA was obtained from 36 SRS patients with hypomethylation at ICR1. All CTCFL coding exons were sequenced and analyzed for duplications/deletions using both multiplex ligation-dependent probe amplification, with a custom CTCFL probe set, and genomic qPCR. Novel SNP alleles were analyzed for potential differential splicing in vitro utilizing a splicing assay. Neither mutations of CTCFL nor duplications/delet