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

BMC Medical Genetics

Edwin A Mitchell³  Jörg Tost²  John MD Thompson³  Rinki Murphy¹ 

[1] Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand;Laboratory for Epigenetics and Environment, Centre National de Genotypage, CEA-Institut de Genomique, Evry, France;Department of Paediatrics, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

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

Others  :  1091470
DOI  :  10.1186/1471-2350-15-67

 received in 2014-02-07, accepted in 2014-06-11,  发布年份 2014

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2014 Murphy et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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