The imprinted human 11p15.5 region encompasses two imprinted domains important for the control of fetal growth: the H19/IGF2 domain in the telomeric region and the KCNQ1OT1/CDKN1C domain in the centromeric region. These two domains are differentially methylated and each is regulated by its own imprinting control region (ICR): ICR1 in the telomeric region and ICR2 in the centromeric region. Aberrant methylation of the 11p15.5 imprinted region, through genetic or epigenetic mechanisms, leads to two clinical syndromes, with opposite growth phenotypes: Russell–Silver Syndrome (RSS; with severe fetal and postnatal growth retardation) and Beckwith–Wiedemann Syndrome (BWS; an overgrowth syndrome).
In this review, we discuss the recently identified molecular abnormalities at 11p15.5 involved in RSS and BWS, which have led to the identification of cis-acting elements and trans-acting regulatory factors involved in the regulation of imprinting in this region. We also discuss the multilocus imprinting disorders identified in various human syndromes, their clinical outcomes and their impact on commonly identified metabolism disorders.
These new findings and progress in this field will have direct consequence for diagnostic and predictive tools, risk assessment and genetic counseling for these syndromes.
aAP-HP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes
bUPMC Paris 6, UMR_S938, Centre de Recherche de Saint-Antoine
cINSERM, UMR_S938, Centre de Recherche de Saint-Antoine, Paris, France
Correspondence to Irène Netchine, Explorations Fonctionnelles Endocriniennes, Hôpital Armand Trousseau, Pierre & Marie Curie School of Medicine, INSERM UMR-S938, 26 Av du Dr Arnold Netter, 75012, France. Tel.: +33 144736448;. fax: +33 144736621; e-mail: firstname.lastname@example.org