A novel GHR intronic variant, c.266+83G>T , activates a cryptic 5' splice site causing severe GHR deficiency and classical GH insensitivity syndrome.

Background/aims: Mutations in the human growth hormone receptor gene (GHR) are the most common cause of growth hormone insensitivity (GHI) syndrome and insulin-like growth factor (IGF-1) deficiency. The extracellular domain of GHR (encoded by exons 2-7 of the GHR gene) can be proteolytically cleaved to circulate as GH-binding protein (GHBP).

Methods: We evaluated the cause of classical GHI (Laron) phenotypes in 3 siblings.