title: A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis.
abstract: BACKGROUND
  Thyroid dysgenesis is the most frequent cause of congenital hypothyroidism (CH), and its genetic basis is largely unknown. Hitherto, two mutations in the human thyroid transcription factor 2 (TTF-2) gene have been described in unrelated cases of CH with cleft palate, spiky hair, variable choanal atresia, and complete thyroid agenesis. Here, we describe a novel TTF-2 mutation in a female child resulting in syndromic CH in the absence of thyroid agenesis.
  
  
  RESULTS
  The index case is homozygous for an arginine to cysteine mutation (R102C) of a highly conserved residue within the forkhead, DNA binding domain of TTF-2. Her consanguineous, heterozygous parents are unaffected, and the mutation was not detected in 100 control chromosomes. Consonant with its location, the R102C mutant TTF-2 protein showed loss of DNA binding and was transcriptionally inactive. CH in the proposita was associated with cleft palate, spiky hair, and bilateral choanal atresia. However, radiological studies showed the presence of thyroid tissue in a eutopic location.
  
  
  CONCLUSIONS
  Our findings indicate that human thyroid development can occur despite loss of TTF-2 function and suggest that TTF-2 gene defects should also be considered in cases of syndromic CH without total athyreosis.
authors.affiliation: Boğaziçi University, Department of Molecular Biology and Genetics, Bebek, 34342 Istanbul, Turkey.
authors.forename: I
authors.initials: I
authors.lastname: Baris
authors.forename: A E
authors.initials: AE
authors.lastname: Arisoy
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Agostini
authors.forename: C S
authors.initials: CS
authors.lastname: Mitchell
authors.forename: S M
authors.initials: SM
authors.lastname: Park
authors.forename: A M
authors.initials: AM
authors.lastname: Halefoglu
authors.forename: E
authors.initials: E
authors.lastname: Zengin
authors.forename: V K
authors.initials: VK
authors.lastname: Chatterjee
authors.forename: E
authors.initials: E
authors.lastname: Battaloglu
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D013961:Thyroid Gland / Q000002:abnormalities*
chemical_list: C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors