Fig. 3

Molecular mechanism of Silver–Russell syndrome. a Loss of methylation (LOM) at differentially methylated region 1 (DMR1) on the paternal chromosome results in expression of H19 and downregulation of IGF2. b Maternal uniparental disomy (UPD) occurs when a patient has two copies of the maternal chromosome and none of the paternal chromosome. Maternal UPD 11p15 results in downregulation of IGF2 in addition to overexpression of KCNQ1 and CDKN1C. c CDKN1C gain-of-function mutations on the maternal chromosome and d IGF2 loss-of-function mutations on the paternal chromosome also result in Silver–Russell syndrome. Green triangles indicate enhancers. Lollipops indicate methylated imprinting centers. Genes normally expressed from the maternal chromosome are depicted as red boxes, and genes normally expressed from the paternal chromosome are depicted as blue boxes. Arrows indicate the orientation of transcription. M = maternal. P = paternal. Tel = telomere. Cen = centromere