title: Phenotypic variation among four family members with congenital hypothyroidism caused by two distinct thyroglobulin gene mutations.
abstract: BACKGROUND
  Thyroglobulin (Tg) is a large glycoprotein that is intimately involved in the biosynthesis of thyroxine and triiodothyronine. At least 38 mutations have been described in the Tg gene that are associated with varying degrees of hypothyroidism. We studied the Tg gene in four related subjects with congenital hypothyroidism.
  
  
  CONCLUSIONS
  We found a novel compound heterozygous constellation (IVS30 + 1G>T/A2215D) in a brother and sister and one previously described related mutation (IVS30+1G>T) in their two sibling second degree cousins. The brother with the IVS30 + 1G>T/A2215D mutation and the two siblings with the IVS30+1G>T mutation had fetal or neonatal goiter and all had hypothyroidism.
  
  
  CONCLUSIONS
  This study further confirms the association of the IVS30+G>T mutation of the Tg gene with hypothyroidism. Computer analysis predicts that the A2215D mutation, first reported here, should cause structural instability of Tg but when present as a compound heterozygous mutation with IVS30+G>T/A its effect is unclear but is likely to be influenced by iodine intake.
authors.affiliation: Thyroid Study Unit (LIM-25), Division of Endocrinology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Viviane
authors.initials: V
authors.lastname: Pardo
authors.forename: Ileana G S
authors.initials: IG
authors.lastname: Rubio
authors.forename: Meyer
authors.initials: M
authors.lastname: Knobel
authors.forename: Manoel H
authors.initials: MH
authors.lastname: Aguiar-Oliveira
authors.forename: Marcos M
authors.initials: MM
authors.lastname: Santos
authors.forename: Simone A
authors.initials: SA
authors.lastname: Gomes
authors.forename: Carla R P
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Hector M
authors.initials: HM
authors.lastname: Targovnik
authors.forename: Geraldo
authors.initials: G
authors.lastname: Medeiros-Neto
mesh_terms: D001938:Brazil; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013954:Thyroglobulin / Q000097:blood / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine