title: A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency.
abstract: PIT1 abnormality is defined as a genetic abnormality in 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 reported in several cases. We studied the PIT1 gene in a patient with combined deficiency of TSH, GH and PRL. A novel mutation substituting a termination codon for Glutamate at 250th codon (E250X) was identified in the homozygous state in the patient. Both of the healthy parents harbored this mutation in the heterozygous state. This nonsense mutation results in complete loss of helix 3 of the POU homeodomain of Pit-1/GHF-1. As helix 3 of the homeodomain is involved directly in 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 PRL in this patient.
authors.affiliation: Department of Laboratory Medicine, Osaka University Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Irie
authors.forename: K
authors.initials: K
authors.lastname: Tatsumi
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: T
authors.initials: T
authors.lastname: Kamijo
authors.forename: C
authors.initials: C
authors.lastname: Preeyasombat
authors.forename: C
authors.initials: C
authors.lastname: Suprasongsin
authors.forename: N
authors.initials: N
authors.lastname: Amino
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D010907:Pituitary Hormones / Q000172:deficiency* / Q000235:genetics*; D017354:Point Mutation; D011388:Prolactin / Q000172:deficiency / Q000235:genetics; D013972:Thyrotropin / Q000172:deficiency / Q000235:genetics; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D010907:Pituitary Hormones; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone