Journal article

Analysis of the IGF2/H19 imprinting control region uncovers new genetic defects, including mutations of OCT-binding sequences, in patients with 11p15 fetal growth disorders

J Demars, ME Shmela, S Rossignol, J Okabe, I Netchine, S Azzi, S Cabrol, C le Caignec, A David, Y le Bouc, A El-Osta, C Gicquel

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2010

Abstract

The imprinted expression of the IGF2 and H19 genes is controlled by the imprinting control region 1 (ICR1) located at chromosome 11p15.5. This methylation-sensitive chromatin insulator works by binding the zinc-finger protein CTCF in a parent-specific manner. DNA methylation defects involving the ICR1 H19/IGF2 domain result in two growth disorders with opposite phenotypes: an overgrowth disorder, the Beckwith-Wiedemann syndrome (maternal ICR1 gain of methylation in 10% of BWS cases) and a growth retardation disorder, the Silver-Russell syndrome (paternal ICR1 loss of methylation in 60% of SRS cases). Although a few deletions removing part of ICR1 have been described in some familial BWS case..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (Project grant 472637), the Baker IDI Heart and Diabetes Institute, the Institut National de la Sante et de la Recherche Medicale UMPC U938, Universite 'Pierre et Marie Curie Paris 6 and Assistance Publique Hopitaux de Paris. M. E. S. received funding from the Libyan government.