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.
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.
Blankenstein
O
O
Kinderklinik, Universitätsklinikum der RWTH Aachen, Deutschland. oblankenstein@post.klinikum.rwth-aachen.de
Mühlenberg
R
R
Kim
C
C
Wüller
S
S
Pfäffle
R
R
Heimann
G
G
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*
D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D014157:Transcription Factors