title: Segmental maternal uniparental disomy 7q associated with DLK1/GTL2 (14q32) hypomethylation.
abstract: Aberrant methylation at different imprinted loci has been reported for several congenital imprinting disorders, that is, Silver-Russell syndrome (SRS), but the coincidental occurrence of aberrant methylation and uniparental disomy (UPD) has not yet been described. We report on a patient initially diagnosed with SRS carrying a segmental maternal UPD of chromosome 7 [upd(7q)mat]. By further screening the patient's DNA for methylation defects on other chromosomes we identified a hypomethylation of the paternally methylated DLK1/GTL2 locus in 14q32, an epigenotype typically associated with the upd(14)mat phenotype. Detailed clinical analysis confirmed the molecular finding in the patient indicating that the 14q32 epimutation was clinically preponderant. The parallel occurrence of upd(7q)mat and a DLK1/GTL2 hypomethylation in the same patient is a unique finding. Indeed, both disturbances might have occurred coincidentally, but it can also be hypothesized that the upd(7q)mat as the initial genomic mutation represents a trans-acting mutation causing an aberrant methylation in 14q32.
authors.affiliation: Institut für Humangenetik, RWTH, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Begemann
authors.forename: Sabrina
authors.initials: S
authors.lastname: Spengler
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kordass
authors.forename: Carmen
authors.initials: C
authors.lastname: Schröder
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
mesh_terms: D002135:Calcium-Binding Proteins; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D002897:Chromosomes, Human, Pair 7; D019175:DNA Methylation / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding; D056730:Silver-Russell Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D024182:Uniparental Disomy / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C498907:MEG3 non-coding RNA, human; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding