Title:Human Imprinting Anomalies in Fetal and Childhood Growth Disorders: Clinical Implications and Molecular Mechanisms
Volume: 20
Issue: 11
Author(s): Salah Azzi, Frederic Brioude, Yves Le Bouc and Irene Netchine
Affiliation:
Keywords:
Epigenetic regulation, genomic impirinting, human impriting syndrome, growth disorders, RSS, BWS, PHP-1b, AS, PWS,
TNDM, chromosome 14 related syndromes.
Abstract: Genomic imprinting is among the most important epigenetic mechanisms whereby expression of a subset of genes is restricted
to a single parental allele. Loss of imprinting (LOI) through hypo or hyper methylation is involved in various human syndromes. These
LOI occur early during development and usually impair growth. Some imprinting syndromes are the consequences of genetic anomalies,
such as uniparental disomies (UPD) or copy number variations (deletion or duplications) involving the imprinted domains; others are due
to LOI at the imprinting control regions (ICR) regulating each domain. Imprinting disorders are phenotypically heterogeneous, although
some share various common clinical features such that diagnosis may be difficult. Multilocus imprinting defects associated with several
syndromes have been increasingly reported in recent years, although there are no obvious clinical differences between monolocus and
multilocus LOI patients. Subsequently, some rare mutations of transacting factors have been identified in patients with multilocus imprinting
defects but they do not explain the majority of the cases; this therefore implies that other factors are involved. By contrast, no
mutation of a transacting factor has yet been identified in monolocus LOI. The effect of the environment on the regulation of imprinting
is clearly illustrated by studies of assisted reproductive technology (ART). The regulation of imprinting is complex and involves a huge
range of genetic and environmental factors; the identification of these factors will undoubtedly help to elucidate the regulation of imprinting
and contribute to the understanding of imprinting disorders. This would be beneficial for diagnostics, clinical follow up and the development
of treatment guidelines.
