title: The C105fs114X is the prevalent thyrotropin beta-subunit gene mutation in Argentinean patients with congenital central hypothyroidism.
abstract: BACKGROUND
  Congenital isolated thyrotropin (TSH) deficiency is an unusual condition characterized by low levels of thyroid hormones and TSH, usually presenting early typical signs of severe hypothyroidism. Five different beta-TSH mutations have been described so far. While 4 of them affect only consanguineous families, a frameshift mutation in exon 3 (C105fs114X) has been found also in nonconsanguineous families.
  
  
  OBJECTIVE
  The aim of the present study was to characterize beta-TSH mutations in Argentinean patients with congenital central hypothyroidism (CCH) and to emphasize the importance of early biochemical and molecular diagnosis of this disorder.
  
  
  METHODS
  We investigated 8 Argentinean children (3 boys, 5 girls) from 7 unrelated families with CCH based upon low levels of T(4) and T(3), and low basal and stimulated TSH levels. Mutation characterizations for the beta-TSH gene were performed by PCR amplification followed by sequence and restriction enzyme analysis with SNABI in the patients, 9 parents and in 100 newborn children.
  
  
  RESULTS
  All patients presented the same homozygous mutation in exon 3 of the beta-TSH gene (C105fs114X), the 9 studied parents were heterozygous for the same mutation and 1 carrier was found in the 100 studied newborns.
  
  
  CONCLUSIONS
  Our findings show that the C105fs114X mutation is prevalent in our population and may constitute a hot spot at codon 105 in the beta-TSH gene. Since this mutation is easily demonstrable by a SNABI digestion in DNA amplified from dried blood spots, its investigation would be indicated in patients in our milieu with clinical and biochemical features of CCH, allowing early L-thyroxine (LT(4)) replacement and genetic counseling of the family.
authors.affiliation: División de Endocrinología, Centro de Investigaciones Endocrinológicas, Hospital de Niños 'R. Gutiérrez', Buenos Aires, Argentina. hdomene@cedie.org.ar
authors.forename: Horacio M
authors.initials: HM
authors.lastname: Domené
authors.forename: Laura
authors.initials: L
authors.lastname: Gruñeiro-Papendieck
authors.forename: Ana
authors.initials: A
authors.lastname: Chiesa
authors.forename: Sonia
authors.initials: S
authors.lastname: Iorcansky
authors.forename: Viviana C
authors.initials: VC
authors.lastname: Herzovich
authors.forename: Regina
authors.initials: R
authors.lastname: Papazian
authors.forename: Verónica
authors.initials: V
authors.lastname: Forclaz
authors.forename: Laura
authors.initials: L
authors.lastname: Prieto
authors.forename: Gabriela
authors.initials: G
authors.lastname: Sansó
authors.forename: Paula
authors.initials: P
authors.lastname: Scaglia
authors.forename: Mónica
authors.initials: M
authors.lastname: Bre
authors.forename: Alfredo
authors.initials: A
authors.lastname: Chamoux
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Heinrich
mesh_terms: D002648:Child; D003409:Congenital Hypothyroidism; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis* / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D037322:Thyrotropin, beta Subunit / Q000172:deficiency* / Q000235:genetics*
chemical_list: D037322:Thyrotropin, beta Subunit