Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci.
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.
Turner
Claire Louise Susan
CL
Academic Unit of Genetic Medicine, School of Medicine, University of Southampton, Princess Anne Hospital, Southampton, UK.
Mackay
Deborah M
DM
Callaway
Jonathan L A
JL
Docherty
Louise E
LE
Poole
Rebecca L
RL
Bullman
Hilary
H
Lever
Margaret
M
Castle
Bruce M
BM
Kivuva
Emma C
EC
Turnpenny
Peter D
PD
Mehta
Sarju G
SG
Mansour
Sahar
S
Wakeling
Emma L
EL
Mathew
Verghese
V
Madden
Jackie
J
Davies
Justin H
JH
Temple
I Karen
IK
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
C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D017527:Receptor, IGF Type 2