Two new PROP1 gene mutations responsible for compound pituitary hormone deficiency.

Mutations in the Prophet of Pit-1 (Prop-1), a paired-like homeodomain transcription factor involved in the early embryonic pituitary development, have been reported as a cause of combined hormone deficiency (CPHD) involving growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), gonadotrophins and in some cases adrenocorticotrophic hormone (ACTH). We report two pre-pubertal siblings with short stature and deficiency of GH and TSH at presentation. Molecular analysis of the PROP1 gene revealed compound heterozygotes for two novel missense mutations of the PROP1 gene affecting the same amino acid (Arg71Cys and Arg71His) in the first alpha helix of the Prop-1 homeodomain.