title: A mutational hot spot in the Prop-1 gene in Russian children with combined pituitary hormone deficiency.
abstract: Combined pituitary hormone deficiency (CPHD), including growth hormone (GH), prolactin (Prl) and thyroid-stimulating hormone (TSH) in children is now considered a heterogeneous syndrome. Recent findings on expression of mouse pituitary-specific homeodomain factors demonstrate dependence of adenopituitary ontogeny on interactive expression of these factors, suggesting their involvement in etiology of CPHD. Prophet of Pit-1 (Prop-1) gene, a novel pituitary-specific homeodomain factor, was analyzed in 14 Russian children with CPHD, in whom Pit-1 gene was intact. We found a mutational hot spot in three patients from two families in homeodomain part of the second exon of Prop-1 gene. The common 2-base pair deletion (GA296) in the homozygous state resulted in a Serine to Stop codon (S109X) substitution and generated a truncated Prop-1 protein. Parents were phenotypically normal and heterozygous for GA296 deletion, indicating an autosomal recessive inheritance. These results demonstrate a novel type of Prop-1 gene mutation as one of the causes of CPHD in Russian patients.
authors.affiliation: Department of Pediatrics, Endocrinology Research Center, Moscow, Russia.
authors.forename: O V
authors.initials: OV
authors.lastname: Fofanova
authors.forename: N
authors.initials: N
authors.lastname: Takamura
authors.forename: E
authors.initials: E
authors.lastname: Kinoshita
authors.forename: J S
authors.initials: JS
authors.lastname: Parks
authors.forename: M R
authors.initials: MR
authors.lastname: Brown
authors.forename: V A
authors.initials: VA
authors.lastname: Peterkova
authors.forename: O V
authors.initials: OV
authors.lastname: Evgrafov
authors.forename: N P
authors.initials: NP
authors.lastname: Goncharov
authors.forename: A A
authors.initials: AA
authors.lastname: Bulatov
authors.forename: I I
authors.initials: II
authors.lastname: Dedov
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D018398:Homeodomain Proteins / Q000235:genetics*; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D010375:Pedigree; D010907:Pituitary Hormones / Q000172:deficiency*; D011388:Prolactin / Q000172:deficiency; D012426:Russia; D017384:Sequence Deletion; D013577:Syndrome; D013972:Thyrotropin / Q000172:deficiency
chemical_list: D018398:Homeodomain Proteins; D010907:Pituitary Hormones; C102134:Prophet of Pit-1 protein; D019382:Human Growth Hormone; D011388:Prolactin; D013972:Thyrotropin