title: Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci.
abstract: This study was an investigation of 79 patients referred to the Wessex Regional Genetics Laboratory with suspected Russell-Silver Syndrome or unexplained short stature/intra uterine growth restriction, warranting genetic investigation. Methylation status was analysed at target sequences within eleven imprinted loci (PLAGL1, IGF2R, PEG10, MEST1, GRB10, KCNQ1OT1, H19, IGF2P0, DLK1, PEG3, NESPAS). Thirty seven percent (37%) (29 of 79) of samples were shown to have a methylation abnormality. The commonest finding was a loss of methylation at H19 (23 of 29), as previously reported in Russell-Silver Syndrome. In addition, four of these patients had methylation anomalies at other loci, of whom two showed hypomethylation of multiple imprinted loci, and two showed a complete gain of methylation at IGF2R. This latter finding was also present in five other patients who did not have demonstrable changes at H19. In total, 7 of 79 patients showed a gain of methylation at IGF2R and this was significantly different from a normal control population of 267 individuals (P=0.002). This study in patients with growth restriction shows the importance of widening the epigenetic investigation to include multiple imprinted loci and highlights potential involvement of the IGF2R locus.
authors.affiliation: Academic Unit of Genetic Medicine, School of Medicine, University of Southampton, Princess Anne Hospital, Southampton, UK.
authors.forename: Claire Louise Susan
authors.initials: CL
authors.lastname: Turner
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Mackay
authors.forename: Jonathan L A
authors.initials: JL
authors.lastname: Callaway
authors.forename: Louise E
authors.initials: LE
authors.lastname: Docherty
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Poole
authors.forename: Hilary
authors.initials: H
authors.lastname: Bullman
authors.forename: Margaret
authors.initials: M
authors.lastname: Lever
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Castle
authors.forename: Emma C
authors.initials: EC
authors.lastname: Kivuva
authors.forename: Peter D
authors.initials: PD
authors.lastname: Turnpenny
authors.forename: Sarju G
authors.initials: SG
authors.lastname: Mehta
authors.forename: Sahar
authors.initials: S
authors.lastname: Mansour
authors.forename: Emma L
authors.initials: EL
authors.lastname: Wakeling
authors.forename: Verghese
authors.initials: V
authors.lastname: Mathew
authors.forename: Jackie
authors.initials: J
authors.lastname: Madden
authors.forename: Justin H
authors.initials: JH
authors.lastname: Davies
authors.forename: I Karen
authors.initials: IK
authors.lastname: Temple
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics; D018392:Genomic Imprinting / Q000502:physiology; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics; D017422:Sequence Analysis, DNA; D056730:Silver-Russell Syndrome / Q000235:genetics
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D017527:Receptor, IGF Type 2