TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothyroidism

J Endocrinol Invest. 2003 Oct;26(10):997-1000. doi: 10.1007/BF03348198.


The prevalence of thyroid diseases in children with Down's syndrome (DS) is about 3%. The most frequently observed condition is autoimmune subclinical hypothyroidism (SH). Autoimmune SH must be distinguished from defects in the biological activity of the TSH molecule or from the rare inherited condition of thyroid resistance to TSH. To investigate this last aspect we studied 12 patients with DS that had moderately elevated TSH with normal free thyroid hormones without signs of autoimmunity. For the genetic analysis the genomic DNA was extracted from peripheral lymphocytes. All the exons of the TSH receptor (TSHr) and Gs(alpha) genes were sequenced. The genetic analysis of the TSHr gene revealed the presence of four polymorphic variants. In two patients there was an allelic variant in the exon 1 (Pro52Thr--in one patient in the heterozygous state and in the other as a homozygous substitution). In one patient there was an allelic variant in the exon 1 (Asp36His) in the heterozygous state. In 11 patients there was a silent polymorphism in the exon 7 at nucleotide 561. All patients were homozygous for a silent polymorphism in the exon 9 at nucleotide 855. No inactivating mutations of TSHr or Gs(alpha) genes were identified in the 12 patients. In conclusion, our results seem to exclude the role of TSHr or Gs(alpha) gene mutations in the pathogenesis of the non-autoimmune SH observed in some children with DS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • DNA / chemistry
  • DNA / genetics
  • Down Syndrome / complications*
  • Down Syndrome / genetics
  • Female
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Humans
  • Hypothyroidism / complications*
  • Hypothyroidism / genetics
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics
  • Receptors, Thyrotropin / genetics*
  • Sequence Analysis, DNA
  • Thyroid Function Tests


  • Receptors, Thyrotropin
  • DNA
  • GTP-Binding Protein alpha Subunits, Gs