title: Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency.
abstract: Prop-1 is a newly isolated pituitary-specific paired-like homeodomain transcription factor whose cDNA sequence is well known in mouse. To study its involvement in human combined pituitary hormone deficiency (CPHD), we have isolated the human cDNA ortholog and determined the exon/intron organization and chromosomal localization of the human gene. A Prop-1 defect was characterized in three CPHD families. One missense mutation (R73C) involves a residue conserved in 95% of the more than 400 homeodomain proteins so far identified; in vitro splicing assays demonstrated the functional importance of the second defect, whereas the remaining mutation is a frameshift. Given the disease phenotype documented in the patients, these data, which will facilitate molecular investigations in other patients, demonstrate the crucial role of Prop-1 in the proper development of somatotrophs, lactotrophs, thyreotrophs and gonadotrophs.
authors.affiliation: Laboratoire de Génétique, INSERM U.468, Hôpital Mondor, Créteil, France.
authors.forename: P
authors.initials: P
authors.lastname: Duquesnoy
authors.forename: A
authors.initials: A
authors.lastname: Roy
authors.forename: F
authors.initials: F
authors.lastname: Dastot
authors.forename: I
authors.initials: I
authors.lastname: Ghali
authors.forename: C
authors.initials: C
authors.lastname: Teinturier
authors.forename: I
authors.initials: I
authors.lastname: Netchine
authors.forename: V
authors.initials: V
authors.lastname: Cacheux
authors.forename: M
authors.initials: M
authors.lastname: Hafez
authors.forename: N
authors.initials: N
authors.lastname: Salah
authors.forename: J L
authors.initials: JL
authors.lastname: Chaussain
authors.forename: M
authors.initials: M
authors.lastname: Goossens
authors.forename: P
authors.initials: P
authors.lastname: Bougnères
authors.forename: S
authors.initials: S
authors.lastname: Amselem
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D003241:Consanguinity; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000302:isolation & purification; D005091:Exons; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010907:Pituitary Hormones / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D018398:Homeodomain Proteins; D010907:Pituitary Hormones; C102134:Prophet of Pit-1 protein