Open Access Research article

No evidence for copy number and methylation variation in H19 and KCNQ10T1 imprinting control regions in children born small for gestational age

Rinki Murphy1*, John MD Thompson2, Jörg Tost3, Edwin A Mitchell2 and on behalf of the Auckland Birthweight Collaborative Study Group

Author Affiliations

1 Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand

2 Department of Paediatrics, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

3 Laboratory for Epigenetics and Environment, Centre National de Genotypage, CEA-Institut de Genomique, Evry, France

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BMC Medical Genetics 2014, 15:67  doi:10.1186/1471-2350-15-67

Published: 17 June 2014



There is a substantial genetic component for birthweight variation, and although there are known associations between fetal genotype and birthweight, the role of common epigenetic variation in influencing the risk for small for gestational age (SGA) is unknown. The two imprinting control regions (ICRs) located on chromosome 11p15.5, involved in the overgrowth disorder Beckwith-Wiedemann syndrome (BWS) and the growth restriction disorder Silver-Russell syndrome (SRS), are prime epigenetic candidates for regulating fetal growth. We investigated whether common variation in copy number in the BWS/SRS 11p15 region or altered methylation levels at IGF2/H19 ICR or KCNQ10T1 ICR was associated with SGA.


We used a methylation-specific multiplex-ligation-dependent probe amplification assay to analyse copy number variation in the 11p15 region and methylation of IGF2/H19 and KCNQ10T1 ICRs in blood samples from 153 children (including 80 SGA), as well as bisulfite pyrosequencing to measure methylation at IGF2 differentially methylated region (DMR)0 and H19 DMR.


No copy number variants were detected in the analyzed cohort. Children born SGA had 2.7% lower methylation at the IGF2 DMR0. No methylation differences were detected at the H19 or KCNQ10T1 DMRs.


We confirm that a small hypomethylation of the IGF2 DMR0 is detected in peripheral blood leucocytes of children born SGA at term. Copy number variation within the 11p15 BWS/SRS region is not an important cause of non-syndromic SGA at term.

DNA methylation; Imprinting; ICR2; ICR1; H19; KCNQ10T1; Small for gestational age