title: A large deletion of PROP1 gene in patients with combined pituitary hormone deficiency from two unrelated Chinese pedigrees.
abstract: BACKGROUND
  Familial combined pituitary hormone deficiency (CPHD) appears to have a genetic cause, PROP1 gene mutations being the most common one. We investigated whether PROP1 plays a role in two Chinese familial cases of CPHD.
  
  
  METHODS
  PROP1 gene and adjacent sequences from genomic samples from two unrelated families were amplified to investigate molecular variations and define the extension of a potential deletion. A quantitative real-time polymerase chain reaction was conducted to analyze the copy number of PROP1 gene in the probands' mothers. The relationship of the two distantly located families was further analyzed using microsatellite markers.
  
  
  RESULTS
  A segment of about 53.2 kilobases (kb) comprehending PROP1 and another gene encoding a hypothetical protein Q6ZTH3 was deleted in both pedigrees. The mother of one of the probands was hemizygous for this large deletion, which confirmed the assumption that the affected children inherited the deletion allele from their consanguineous parents. The difference of three microsatellites surrounding the absent segment indicated that the two pedigrees were genetically unrelated.
  
  
  CONCLUSIONS
  We report the largest genomic deletion including PROP1 gene associated with CPHD. Q6ZTH3 is unlikely to exert an indispensable function during embryogenesis or organogenesis. The 7.7-kb segment upstream of the transcription of PROP1 probably harbors a fragile site that favors the occurrence of breakpoints.
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Lianshu
authors.initials: L
authors.lastname: Han
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gu
authors.forename: Dingping
authors.initials: D
authors.lastname: Shi
mesh_terms: D000293:Adolescent; D002681:China; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004393:Dwarfism, Pituitary / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics*; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D010907:Pituitary Hormones / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D013974:Thyroxine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; D010907:Pituitary Hormones; C102134:Prophet of Pit-1 protein; D019382:Human Growth Hormone; D004247:DNA; D013974:Thyroxine