ABSTRACT
Acknowledgments........................................................................................................................... 60 References ....................................................................................................................................... 60
Imprinted genes are monoallelically expressed from either the maternally or paternally inherited allele. The crucial nature of this regulation is reflected in phenotypic manifestations in individuals exhibiting improper imprinted gene expression. This is evident in a number of human syndromes, including Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS), where genetic or epigenetic lesions disrupt appropriate imprinted gene regulation. Clinically, BWS is characterized by large size at birth, neonatal hypoglycemia, minor dysmorphic features, and increased risk of several types of major organ tumors, including Wilms tumor [1]. SRS describes a uniform malformation syndrome characterized by pre-and postnatal growth restriction [2]. Diagnosis can be difficult and at least four of the following criteria should be present: intrauterine growth retardation, poor postnatal growth, relatively normal head circumference, classic facial phenotype, and asymmetry [2]. Further evidence for the necessity of maintaining the delicate balance of imprinted gene regulation is provided by the widespread and frequent occurrence of loss of imprinting (LOI) in human cancers. LOI denotes loss of monoallelic expression, regardless of the mechanism. Therefore, research into the molecular mechanisms that regulate imprinting is not strictly an academic study of expression modulation, but may have clinical benefits to patients with imprinting dysfunction. The precise imprinted genes and tumor types exhibiting LOI are discussed in more detail below.
