Biallelic expression of IGFBP1 and IGFBP3, two candidate genes for the Silver-Russell syndrome

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Abstract
Editor—Silver-Russell syndrome (SRS) is a condition characterised by intrauterine and postnatal growth retardation with relative sparing of cranial growth, triangular facies, fifth finger clinodactyly, and facial, limb, or truncal asymmetry.1 2 The molecular basis of SRS remains elusive and seems likely to be heterogeneous. However, maternal uniparental disomy of chromosome 7 (mUPD7) has been found in approximately 10% of SRS patients, suggesting that at least one gene on chromosome 7 is imprinted and involved in the pathogenesis of this condition.3 4 Interest has surrounded the human chromosomal region 7p12-13, which is homologous to mouse proximal chromosome 11, since mUPD for this region in mice leads to prenatal growth failure.5 Within this region lie the genes for insulin-like growth factor binding proteins 1 and 3 ( IGFBP1 and IGFBP3 ). Both are involved in regulation of fetal growth via the insulin-like growth factor axis.6 IGFBP1 and IGFBP3 are therefore obvious candidates for a role in the SRS phenotype associated with mUPD7.3 4 In order to determine whether IGFBP1 and/or IGFBP3 are likely to be implicated in SRS, we have investigated their imprinting status in normal fetal tissues collected from termination of pregnancies. Samples were obtained from Queen Charlotte's and Chelsea Hospital with the approval of the Research Ethics Committee of the Royal Postgraduate Medical School (96/4955) and from the MRC Tissue Bank at Hammersmith Hospital (L Wong). Genomic DNA and total RNA was extracted from these tissues and RT-PCR performed as previously described.7 The primers used in this study are listed in table 1. PCR was carried out for 35 cycles for all reactions. Products were sequenced on an ABI PRISM 377 automated DNA sequencer using the dRhodamine Ampli- Taq …