title: A new C-terminal located mutation (V272ter) in the PIT-1 gene manifesting with severe congenital hypothyroidism. Possible functionality of the PIT-1 C-terminus.
abstract: OBJECTIVE
  We describe a newborn with clinical signs of severe hypothyroidism and combined pituitary hormone deficiency due to a new mutation in the PIT-1 gene.
  
  
  METHODS
  Endocrine stimulation test revealed a deficiency for PRL, TSH and GH, suggesting a defect in the pituitary transcription factor PIT-1. Genetic analysis of the PIT-1 gene was performed by exon-specific PCR, followed by SSCP mutation screening and DNA sequencing of the abnormal migrating fragments.
  
  
  RESULTS
  DNA sequencing revealed a new mutation (V272ter) in direct neighborhood to a known mutational hot spot (R271W) in the C-terminal part of the PIT-1 molecule.
  
  
  CONCLUSIONS
  Whereas the R271W mutation has a dominant negative effect on the mutant protein, the newly described mutation is inherited in an autosomal-recessive way. The biological consequences of these two different mutations are discussed.
authors.affiliation: Kinderklinik, Universitätsklinikum der RWTH Aachen, Deutschland. oblankenstein@post.klinikum.rwth-aachen.de
authors.forename: O
authors.initials: O
authors.lastname: Blankenstein
authors.forename: R
authors.initials: R
authors.lastname: Mühlenberg
authors.forename: C
authors.initials: C
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Wüller
authors.forename: R
authors.initials: R
authors.lastname: Pfäffle
authors.forename: G
authors.initials: G
authors.lastname: Heimann
mesh_terms: D001483:Base Sequence / Q000235:genetics; D003409:Congenital Hypothyroidism; D004268:DNA-Binding Proteins / Q000235:genetics*; D005808:Genes, Recessive; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D014157:Transcription Factors