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J Mol Med (Berl). 2007 Apr;85(4):379-87. Epub 2006 Dec 16.

Elevated placental expression of the imprinted PHLDA2 gene is associated with low birth weight.

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  • 1Translational Research Laboratory, Department of Gynaecological Oncology, The Windeyer Institute of Medical Sciences, 46 Cleveland Street, London, W1T 4JF, UK.


The identification of genes that regulate fetal growth will help establish the reasons for intrauterine growth restriction. Most autosomal genes are expressed biallelically, but some are imprinted, expressed only from one parental allele. Imprinted genes are associated with fetal growth and development. The growth of the fetus in utero relies on effective nutrient transfer from the mother to the fetus via the placenta. Some current research on the genetic control of fetal growth has focused on genes that display imprinted expression in utero. The expression levels of four imprinted genes, the paternally expressed insulin growth factor 2 (IGF2), the mesoderm-specific transcript isoform 1 (MEST); the maternally expressed pleckstrin homology-like domain, family A, member 2 (PHLDA2); and the polymorphically imprinted insulin-like growth factor 2 (IGF2R) gene are all known to have roles in fetal growth and were studied in the placentae of 200 white European, normal term babies. The quantitative expression analysis with real-time PCR showed the maternally expressing PHLDA2 but not the paternally expressing IGF2 and MEST, nor the polymorphic maternally expressing IGF2R placental levels to have a statistically significant effect on birth weight. PHLDA2 expression levels are negatively correlated with size at birth. These data implicate PHLDA2 as an imprinted gene important in fetal growth and also as a potential marker of fetal growth.

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