title: [Molecular pathology of congenital pituitary hypothyroidism--discovery of new clinical entities].
abstract: Congenital pituitary hypothyroidism (pituitary cretinism) results in severe mental and growth retardation when it is not treated soon after birth. Since the introduction of neonatal mass screening of thyrotropin (TSH), most congenital hypothyroidism has been detected except for pituitary and hypothalamic hypothyroidism. In 1971, we reported the first familial case of congenital isolated TSH deficiency and thereafter began intensively investigating the molecular pathology of congenital pituitary hypothyroidism. After determining the entire structure of the human TSH beta gene, we identified the molecular pathology in this patient. Recently, we reported a familial case of congenital combined pituitary hormone deficiency (PIT1 abnormality). To examine the PIT1 gene, which encodes pituitary specific transcription factor, Pit-1/GHF-1, we determined its genomic structure. Sequence comparisons using PCR amplified PIT1 gene sequences revealed only one nonsense mutation in the patient, and established that this alteration caused the combined deficiencies of TSH, GH and PRL. We also discuss other recent progress in molecular pathology of congenital pituitary hypothyroidism.
authors.affiliation: Department of Laboratory Medicine, Osaka University Medical School, Suita.
authors.forename: K
authors.initials: K
authors.lastname: Tatsumi
authors.forename: N
authors.initials: N
authors.lastname: Amino
authors.forename: K
authors.initials: K
authors.lastname: Miyai
mesh_terms: D003409:Congenital Hypothyroidism / Q000151:congenital / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D013006:Growth Hormone / Q000172:deficiency; D006801:Humans; D009154:Mutation; D011388:Prolactin / Q000172:deficiency; D013972:Thyrotropin / Q000172:deficiency / Q000235:genetics; 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; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone