Contribution of GRB10 to the prenatal phenotype in Silver-Russell syndrome? Lessons from 7p12 copy number variations.
Silver-Russell syndrome (SRS) is a congenital disorder characterized by intrauterine growth restriction, poor growth after birth, relatively large head, a triangular face with a prominent forehead, body asymmetry and feeding difficulties. SRS is genetically heterogeneous condition. Significant part of SRS cases are caused by maternal uniparental disomy (UPD) for chromosome 7: condition when both copies of this chromosome (or at least some parts of this chromosome) are of maternal origin. The growth factor binding protein 10 (GRB10) have been thought to be linked to SRS due to its localization of chromosome 7p12, its imprinting status and its assumed role in growth.
Previous studies in UPD mice with chromosome harboring GRB10 showed either growth retardation (when UPD was maternal) or overgrowth (if UPD was paternal).
The authors reported an 18 year old patient who at 7 months old was diagnosed with large head size (>97th percentile), a condition that persisted into adulthood. He was also diagnosed with global development delay and low muscle tone, but had otherwise normal growth. A SNP array was performed and found that the patient had deletion of 7p13p12.1 segment, involving GRB10 and several other genes. It was shown that the paternal allele of GRB10 was deleted in this patient.
Based on data from this patient, the authors concluded that for patients with copy number variations which include the GRB10 gene, the resulting characteristics depend on the size and gene content of the CNV. Maternally inherited GRB10 copy affect prenatal growth, whereas duplications of the maternal copy of the gene or maternal UPD are associated with intrauterine growth retardation. In contrast, a defective GRB10 maternal copy might result in prenatal overgrowth, whereas the paternal GRB10 allele is not required for proper prenatal growth.
Eggermann T. et al. “Contribution of GRB10 to the prenatal phenotype in Silver-Russell syndrome? Lessons from 7p12 copy number variations.” Europ. J. Med. Genetics 2019, v. 62, 103671.
Articles of the month are chosen from newly published genetic research by CDO geneticist, Dr. Iosif Lurie. For more information on any article please contact email@example.com