title: Investigation of 90 patients referred for molecular cytogenetic analysis using aCGH uncovers previously unsuspected anomalies of imprinting.
abstract: This study was an investigation of 90 patients referred to the Wessex Regional Genetics Laboratory for and negative by molecular cytogenetic analysis using array comparative genomic hybridization. This patient cohort represents typical referrals to a regional genetic centre. Methylation analysis was performed at 13 imprinted loci [PLAGL1, IGF2R, MEST, GRB10, H19, IGF2 DMR2 (IGF2P0), KCNQ1OT1 (KvDMR), MEG3, SNRPN, PEG3, GNAS (GNAS exon 1a and NESP55) and GNASAS]. In total 6/90 (6.67%) were shown to have a methylation defect, 2 of which were associated with known imprinting disorders: 1 patient had isolated hypomethylation at IGF2P0, an atypical epigenotype associated with Russell-Silver syndrome, and 1 showed hypomethylation at KvDMR consistent with a diagnosis of Beckwith-Wiedemann syndrome. A further 4 patients, 3 exhibiting complete hypermethylation, and 1 partial hypomethylation, had aberrations at IGF2R, the clinical significance of which remains unclear. This study demonstrates the potential utility of epigenetic investigation in routine diagnostic testing.
authors.affiliation: Division of Human Genetics, University of Southampton School of Medicine, Southampton SO16 6YD, UK. r.l.poole@southampton.ac.uk
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Poole
authors.forename: Emma
authors.initials: E
authors.lastname: Baple
authors.forename: John A
authors.initials: JA
authors.lastname: Crolla
authors.forename: I Karen
authors.initials: IK
authors.lastname: Temple
authors.forename: Deborah J G
authors.initials: DJ
authors.lastname: Mackay
mesh_terms: D000293:Adolescent; D000328:Adult; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism*; D002675:Child, Preschool; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D019175:DNA Methylation; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D056730:Silver-Russell Syndrome / Q000235:genetics*
chemical_list: D015415:Biomarkers