title: A novel nonsense mutation in the Pit-1 gene: evidence for a gene dosage effect.
abstract: The POU transcription factor Pit-1 functions in the development of somatotrophs, lactotrophs, and thyrotrophs of the anterior pituitary gland. It also plays a role in cell-specific gene expression and regulation of the gene products from these cell types, GH, prolactin, and TSH, respectively. In the present report we studied a patient with severe growth failure. Provocative studies revealed undetectable GH, prolactin, and TSH levels, and her pituitary gland was hypoplastic on magnetic resonance imaging. She had a novel homozygous nonsense mutation in the 3' end of the first alpha-helix of the POU-specific domain of the Pit-1 gene. This mutation results in a truncated protein with loss of most of the Pit-1 DNA-binding domains. Interestingly, her parents, who each have one mutant allele, have evidence of mild endocrine dysfunction. Thus, two normal copies of the Pit-1 gene appear necessary for full Pit-1 gene function.
authors.affiliation: Division of Endocrinology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Mariangela
authors.initials: M
authors.lastname: Cisternino
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Cohen
mesh_terms: D002648:Child; D018389:Codon, Nonsense; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D018628:Gene Dosage; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D007223:Infant; D011388:Prolactin / Q000235:genetics; D011401:Promoter Regions, Genetic; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D019382:Human Growth Hormone; D011388:Prolactin; D004247:DNA