Contribution of GRB10 to the prenatal phenotype in Silver-Russell syndrome? Lessons from 7p12 copy number variations.

Abstract

The growth factor binding protein 10 (GRB10) has been suggested as a candidate gene for Silver-Russell syndrome because of its localization in 7p12, its imprinting status, data from mice models and its putative role in growth. Based on a new patient with normal growth carrying a GRB10 deletion affecting the paternal allele and data from the literature, we conclude that the heterogeneous clinical findings in patients with copy number variations (CNVs) of GRB10 gene depend on the size and the gene content of the CNV. However, evidence from mouse and human cases indicate a growth suppressing role of GRB10 in prenatal development. As a result, an increase of active maternal GRB10 copies, e.g. by maternal uniparental disomy of chromosome 7 or duplications of the region results in intrauterine growth retardation. In contrast, a defective GRB10 copy might result in prenatal overgrowth, whereas the paternal GRB10 allele is not required for proper prenatal growth.

• Authors: Thomas Eggermann, Matthias Begemann, Ingo Kurth, Miriam Elbracht
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 62 Issue 7 Pg. 103671 (Jul 2019) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 31100449 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Masson SAS.

Chemical References

• GRB10 protein, human
• GRB10 Adaptor Protein

Topics

• Adolescent
• Chromosomes, Human, Pair 7 (genetics)
• DNA Copy Number Variations
• Fetal Development (genetics)
• GRB10 Adaptor Protein (genetics)
• Humans
• Male
• Phenotype
• Silver-Russell Syndrome (genetics, pathology)