Genetics of human stature: Insight from single gene disorders

Mutations of numerous genes encoding proteins that affect multiple pathways responsible for regulation of cell proliferation can cause growth disturbances in humans. Genes such as HESX1, PROP1, PIT1/POU1F1 and GLI2 have been shown to cause pituitary hormone deficiency. In addition, heterozygous mutations or gene deletions in the growth hormone-insulin-like growth factor (GH-IGF) axis such as the GH, GH-releasing hormone receptor, GH receptor, STAT5b, IGF-I, IGF-I receptor and the acid labile subunit have also been observed in children with growth failure and short stature. More recently, mutations of genes encoding regulators of cell proliferation and division, i.e., the pericentrin gene, have also resulted in severe growth disturbances.