Exhaustive methylation analysis revealed uneven profiles of methylation at IGF2/ICR1/H19 11p15 loci in Russell Silver syndrome

The imprinted 11p15 IGF2/ICR1/H19 domain contains ten differentially methylated loci all methylated on the paternal allele. Hypomethylation at this domain causes Russell Silver Syndrome (RSS), a condition associating severe growth retardation, metabolic disturbances and characteristic dysmorphism. We have exhaustively documented the methylation pattern across the entire IGF2/ICR1/H19 domain in a large cohort of RSS patients carrying 11p15 ICR1 hypomethylation (n =104). For these patients, we found uneven levels of methylation across the domain allowing to distinguish two groups of loci unevenly hypomethylated. Interestingly, 9% of the RSS patients showed normal methylation at some loci of the 11p15 IGF2/ICR1/H19. Our results constitute an important step toward understanding the mechanisms of regulation of the imprinted IGF2/ICR1/H19 domain. These finding are of major diagnostic consequences to design a reliable molecular test for RSS. (By Dr. Salah Azzi, http://jmg.bmj.com/content/early/2014/11/13/jmedgenet-2014-102732 )