Hypomethylation of the MEG8:Int2-DMR in patients with pathogenic PLAG1 variants suggests new role of the chr14q32 imprinting cluster in Silver-Russell syndrome.

ABSTRACT:

Background

Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous imprinting disorder. The most common molecular defects are loss of methylation of the H19/IGF2:IG-DMR on chromosome 11p15.5, followed by maternal uniparental disomy of chromosome 7. Further molecular lesions are genetic variants in the PLAG1 oncogene, as well as in the transcription factor HMGA2 and the fetal growth factor IGF2. A phenotypic overlap exists between SRS and Temple syndrome (TS14) that is also characterized by growth restriction but associated with abnormalities in the imprinted chromosome 14q32 gene cluster. In TS14 patients, the germline MEG3/DLK1: IG-DMR is hypomethylated and the MEG8:Int2-DMR gains methylation probably as consequence of transcriptional readthrough from the MEG3

SUBMITTER: D'Angelo E 

PROVIDER: S-EPMC12764072 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature