title: Germline epimutation in humans.
abstract: Epigenetic modifications provide all multicellular organisms with a system of gene regulation that allows clonally heritable yet reversible alterations in gene transcription. Errors in this complex system can give rise to abnormal gene silencing, termed 'epimutation'; importantly, this can occur in the absence of any underlying genetic defect. Epimutations are commonly somatic events, and are particularly prevalent in tumors, but we and others have shown that epimutation can also arise in the germline, giving rise to soma-wide transcriptional silencing of a gene. A germline epimutation can mimic the effect of an inactivating mutation, and in doing so, can phenocopy a genetic disease. In this article, we will review the recent findings with germline epimutation at the tumor suppressor gene MLH1, discuss the possible etiology of this phenomenon, and the implications of germline epimutation in humans.
authors.affiliation: Molecular Genetics Division, Victor Chang Cardiac Research Institute, Sydney, Australia.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cropley
authors.forename: David I K
authors.initials: DI
authors.lastname: Martin
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Suter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology*; D018095:Germ-Line Mutation; D006801:Humans; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1