title: A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency.
abstract: The pituitary-specific transcription factor Pit-1/GHF1 regulates the expression of PRL, GH, and TSH beta genes through binding to specific regions of the promoters of these genes. Mutations of the Pit-1 gene have been shown to be responsible for a syndrome of combined pituitary hormone deficiency (CPHD), including complete GH and PRL deficiencies and central hypothyroidism. We studied four siblings presenting with CPHD born to healthy consanguinous parents. All four affected children had complete GH deficiency diagnosed in early childhood. They later developed hypothyroidism and were found to have undetectable PRL levels. The pituitary gland was hypoplastic at magnetic resonance examination in one of the patients. Amplification of genomic DNA and subsequent sequencing of the six exons of the Pit-1 gene allowed identification in the four patients with CPHD of an as yet undescribed mutation in exon 3. A substitution of T go G induced a change from a Phe to a Cys residue at position 135 within the hydrophobic core of the POU-specific DNA-binding domain of the Pit-1 protein. All affected children were homozygous for the mutation, whereas the mother was heterozygous, suggesting a recessive mode of inheritance. Molecular studies in other affected families will allow instructive genotype-phenotype correlations concerning the Pit-1 gene.
authors.affiliation: UMR 9941, CNRS-Université de la Méditerranée, Institut Jean-Roche, Faculté de Médecine Nord, Marseille, France.
authors.forename: I
authors.initials: I
authors.lastname: Pellegrini-Bouiller
authors.forename: P
authors.initials: P
authors.lastname: Bélicar
authors.forename: A
authors.initials: A
authors.lastname: Barlier
authors.forename: G
authors.initials: G
authors.lastname: Gunz
authors.forename: J P
authors.initials: JP
authors.lastname: Charvet
authors.forename: P
authors.initials: P
authors.lastname: Jaquet
authors.forename: T
authors.initials: T
authors.lastname: Brue
authors.forename: B
authors.initials: B
authors.lastname: Vialettes
authors.forename: A
authors.initials: A
authors.lastname: Enjalbert
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005796:Genes; D016678:Genome; D006728:Hormones / Q000097:blood; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010902:Pituitary Gland / Q000473:pathology; D010907:Pituitary Hormones / Q000172:deficiency*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D006728:Hormones; D015335:Molecular Probes; C494187:POU1F1 protein, human; D010907:Pituitary Hormones; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D004247:DNA