Growth regulation, imprinted genes, and chromosome 11p15.5.
Genomic imprinting refers to parent-of-origin-specific gene expression. Human chromosome band 11p15.5 houses a large cluster of genes that are imprinted. Dysregulation of this gene cluster is associated with the overgrowth and tumor predisposition syndrome, Beckwith-Wiedemann syndrome. Several genes in this imprinted cluster encode proteins involved in growth regulation, e.g. the paternally expressed IGF2 and the maternally expressed cell-cycle regulator cyclin dependent kinase inhibitor, CDKN1C. Disruption of imprinted gene expression can result from genetic or epigenetic alterations. Genetic alterations such as duplication, deletion, translocation, inversion, and mutation in imprinted regions have been shown to cause disease. In addition, epimutations that are extrinsic to the primary DNA sequence have also been shown to cause disease. These epimutations usually involve gain or loss of methylation at regulatory differentially methylated regions. Recently, several human diseases in addition to Beckwith-Wiedemann syndrome have been reported to have molecular alterations at chromosome 11p15.5. These include isolated hemihyperplasia, Russell-Silver syndrome, and transient neonatal diabetes mellitus. These molecular alterations and their phenotypic effects on growth are discussed.
Smith
Adam C
AC
Institute of Medical Sciences, University of Toronto, Canada.
Choufani
Sanaa
S
Ferreira
Jose C
JC
Weksberg
Rosanna
R
D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D005810:Multigene Family