Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven Middle Eastern children with growth hormone, prolactin, and thyrotropin deficiency

Abstract

Pit-1, a member of the POU-homeo domain protein family, is one of the transcription factors responsible for anterior pituitary development and pituitary-specific gene expression. Here, we describe seven children with GH, PRL, and TSH deficiency from three, reportedly unrelated, Middle Eastern families, harboring a newly recognized Pro- > Ser recessive mutation in codon 239 of the Pit-1 gene. The mutated residue is located at the beginning of the second alpha-helix of the POU-homeodomain and is strictly conserved among all POU proteins. The Pro239Ser mutant binds DNA normally but is unable to stimulate transcription.