Molecular mechanisms regulating phenotypic outcome in paternal and maternal uniparental disomy for chromosome 14

Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1, and maternally expressed genes (MEGs) such as GTL2 (alias, MEG3), RTL1as (RTL1 antisense), and MEG8. Consistent with this, paternal and maternal uniparental disomies for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. In this report, we review the current knowledge about the underlying factors for the development of clinical features in upd(14)pat and upd(14)mat. The data available suggest that the DLK1–GTL2 IG-DMR functions as a regulator for the maternally inherited imprinted region, and that excessive RTL1 expression and decreased DLK1 and RTL1 expression play a major role in the development of upd(14)pat-like and upd(14)mat-like phenotypes, respectively