Overgrowth syndromes and genomic imprinting: from mouse to man.
Beckwith-Wiedemann syndrome (BWS), a human overgrowth syndrome with a complex genetic basis, is caused by alterations to chromosome 11p15, a region subject to genomic imprinting. These alterations include translocations, duplications, single gene mutations of p57KIP2, and increased expression of insulin-like growth factor 2 (IGF2). A phenotypically related X-linked overgrowth syndrome, Simpson Golabi Behmel syndrome (SGBS), is caused by alterations in glypican-3 (GPC3), a molecule that may interact with the gene products identified to be important in generating the BWS phenotype, that is, IGF2 and p57KIP2. The crucial defect in these overgrowth syndromes is likely to be an imbalance in contributions of growth-promoting genes versus growth-inhibitory genes in critical tissues at specific developmental stages. Murine models have been used to study the effects of targeted deletions of the genes p57KIP2 and GPC3, as well as overexpression of IGF2. At this time, there are still many issues which remain to be explored before we can fully understand the molecular basis of BWS and SGBS.
Li
M
M
Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Squire
J A
JA
Weksberg
R
R
D000818:Animals; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004195:Disease Models, Animal; D018392:Genomic Imprinting; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000235:genetics; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics
D050761:Cyclin-Dependent Kinase Inhibitor p57; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D009687:Nuclear Proteins; D011509:Proteoglycans; C493964:CDKN1C protein, human; C493965:Cdkn1c protein, mouse