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Investigation of the GRB2, GRB7, and CSH1 genes as candidates for the Silver-Russell syndrome (SRS) on chromosome 17q
  1. M P Hitchins1,
  2. S Abu-Amero1,
  3. S Apostolidou1,
  4. D Monk1,2,
  5. P Stanier1,
  6. M A Preece2,
  7. G E Moore1
  1. 1Department of Fetal and Maternal Medicine, Institute of Reproductive and Developmental Biology, Imperial College, Faculty of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK
  2. 2Biochemistry, Endocrinology, and Metabolism, Institute of Child Health and Great Ormond Street Hospital for Sick Children, University College London, 30 Guilford Street, London WC1N 1EH, UK
  1. Correspondence to:
 Dr Hitchins, Department of Fetal and Maternal Medicine, 4th Floor IRDB, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK;
 mhitchin{at}hgmp.mrc.ac.uk

https://doi.org/10.1136/jmg.39.3.e13

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    Silver-Russell syndrome (SRS) (MIM 180860) is characterised by intrauterine and postnatal growth restriction, in association with dysmorphic features most frequently including a small triangular facies, skeletal asymmetry, and fifth finger clinodactyly.1–3 The genetic aetiology of SRS is heterogeneous. Maternal uniparental disomy for chromosome 7 (mUPD(7)) occurs in 7-10% of patients,4,5 with strong evidence that disruption of imprinted gene expression, as opposed to mutation of a recessive gene, underlies the SRS phenotype in these cases.6 A SRS-like phenotype has also been associated with ring chromosome 15 with accompanying deletion on 15q,7,8 trisomy 18 mosaicism,9 deletion on 18p,10 and deletion of 8q11-q13.11

    Three SRS cases have been described with disruptions involving distal 17q. These include two unrelated patients with severe SRS bearing reciprocal translocations, with the breakpoints originally assigned to 17q25. In the first case, the proband had an apparently balanced translocation (17;20)(q25;q13), inherited from her clinically normal father.12 The second patient had a de novo translocation (1;17)(q31;q25).13 The breakpoint in this latter case has recently been cloned and more accurately localised to 17q23.3-q24.14 In the third case, a heterozygous deletion of the chorionic somatomammotrophin hormone 1 (CSH1) gene, which is located within the growth hormone and CSH gene cluster on 17q24.1, was identified in a patient with typical SRS. The deletion was inherited from the father, who appeared clinically normal, but had short stature.15 CSH1, otherwise known as placental lactogen, is produced in the syncytiotrophoblast of the placenta and secreted into the maternal and fetal circulation. CSH1 is detectable in maternal serum from 6 weeks post conception, and levels increase linearly during gestation, peaking at about 30 weeks. CSH1 has been used as a marker for placental integrity during pregnancy, and low levels in the maternal serum …

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