Dominant MLH1 epimutation linked to 5'UTR variant c.-27C>A

ABSTRACT: Constitutional epimutations of tumor suppressor genes manifest as promoter methylation and transcriptional silencing of a single allele in normal somatic tissues, thereby predisposing to cancer. Constitutional MLH1 epimutations occur in individuals with young-onset cancer and demonstrate non-Mendelian inheritance through their reversal in the germline. We report a cancer-affected family showing dominant transmission of soma-wide highly mosaic MLH1 methylation and transcriptional repression linked to a particular genetic haplotype. The epimutation was erased in spermatozoa but reinstated in the somatic cells of the next generation. The affected haplotype harbored two single nucleotide substitutions in tandem: c.-27C>A located near the transcription initiation site and c.85G>T. The c.-27C>A

ORGANISM(S): Homo sapiens

SUBMITTER: Megan Hitchins 

PROVIDER: E-GEOD-30348 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress