Imprinting Disorders

Abstract

Abstract Genomic imprinting is an example of epigenetic inheritance in which differences in gene function depend on whether the allele was inherited from the mother or father. Many disorders appear to involve epigenetic alterations to imprinted genes. Genes involved in imprinting play important roles in both pre‐ and post‐natal growth and neurodevelopment. Imprinting disorders include several childhood genetic disorders such as Prader–Willi, Angelman and Beckwith–Wiedemann syndromes, as well as several types of cancer including Wilms tumour. Recent evidence suggests a correlation between assisted reproductive technologies (ART) and imprinting disorders, a phenomenon requiring more in‐depth studies as the prevalence of ART is increasing. The mechanism of normal imprinting as well as its perturbation in disease is becoming understood and amenable to experimentation. Key Concepts: Imprinted genes are expressed in a parent‐of‐origin‐dependent manner. Imprinting disorders result from genetic abnormalities in imprinted genes. Approximately 1% of the human genome is imprinted, a process which occurs during gamete development. Imprinted genes are generally associated with growth, neurodevelopment and epigenetics. The first imprinted genes discovered were IGF2 (paternally expressed) and H19 (maternally expressed), both located at 11p15. There is an imprinted gene cluster located at 15q11–q13, associated with Prader–Willi and Angelman syndromes. Imprinted genes/transcripts within this region include NDN , MAGEL2 , SNURF‐SNRPN , SNORD116 , SNORD115 and UBE3A . Well‐characterised imprinting disorders include Prader–Willi syndrome (PWS), Angelman syndrome (AS), Beckwith–Wiedemann syndrome (BWS), Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP), Silver–Russell syndrome (SRS) and transient neonatal diabetes mellitus (TNDM). Imprinted genes are associated with many types of cancers, primarily due to a process called loss of imprinting (LOI) which leads to aberrant gene expression. Cancers known to be associated with imprinted genes include Wilms tumour in children, and adult cancers of the ovary, lung, colon and liver. The relationship between artificial reproductive technology (ART) and imprinting disorders is currently being investigated. There is evidence to support a correlation between ART and imprinting disorders which result from loss of maternally imprinted genes such as AS and BWS.