A Novel E250X Mutation of the Pit1 Genein a Patient with Combined Pituitary Hormone Deficiency

Abstract

PIT1 abnormality is defined as a genetic abnormalityin the PIT1 gene that encodes a pituitary specific transcription factor, Pit-1/GHF-1. PIT1 abnormality indicates combined deficiency of thyrotropin (TSH), growth hormone (GH) and prolactin (PRL), and has been reportedin several cases. We studied the PIT1 genein a patient with combined deficiency of TSH, GH and PRL. a novel mutation substituting a termination codon for Glutamate at 250th codon (E250X) was identifiedin the homozygous statein the patient. Both of the healthy parents harbored this mutationin the heterozygous state. This nonsense mutation resultsin complete loss of helix 3 of the POU homeodomain of Pit-1/GHF-1. As helix 3 of the homeodomain is involved directlyin DNA binding, the mutant Pit-1/GHF-1 may lose the DNA binding activity of the POU homeodomain and lose its transcriptional activation. the E250X mutation is therefore considered to be the cause of the combined deficiency of TSH, GH and PRLin this patient. © 1995, The Japan Endocrine Society. All rights reserved.