title: Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency.
abstract: To ascertain the molecular background of combined pituitary hormone deficiency, screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency. The group of patients, suspected of PIT1 mutations, consisted of four familial cases (seven patients) and eight sporadic cases. All had complete GH deficiency and complete or partial Prl and TSH deficiency. Direct sequencing of all six exons of PIT1 and its promoter region showed a C to T transition mutation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L). The patient was heterozygous for mutant and normal alleles. The heterozygous P14L mutation was also present in her mother as well as in her maternal aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the father's DNA, suggesting the need for reevaluation of genomic imprinting. In other children of our series, no mutation in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the other negative cases need to be analyzed for another candidate gene responsible for combined GH/Pr/TSH deficiency.
authors.affiliation: Department of Pediatrics, Research Center for Medical Genetics, 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: M
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuji
authors.forename: V A
authors.initials: VA
authors.lastname: Peterkova
authors.forename: O V
authors.initials: OV
authors.lastname: Evgrafov
authors.forename: I I
authors.initials: II
authors.lastname: Dedov
authors.forename: N P
authors.initials: NP
authors.lastname: Goncharov
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004393:Dwarfism, Pituitary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D013006:Growth Hormone / Q000172:deficiency / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D010907:Pituitary Hormones / Q000172:deficiency* / Q000235:genetics; D011388:Prolactin / Q000172:deficiency / Q000502:physiology; D012426:Russia / Q000453:epidemiology; D013972:Thyrotropin / Q000172:deficiency / Q000502:physiology; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C494187:POU1F1 protein, human; D010907:Pituitary Hormones; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone