The R450H mutation and D727E polymorphism of the thyrotropin receptor gene in a Chinese child with congenital hypothyroidism

J Pediatr Endocrinol Metab. 2010 Dec;23(12):1339-44. doi: 10.1515/jpem.2010.209.


Background: Congenital hypothyroidism (CH) is the most prevalent congenital endocrine disorder. The molecular cause of CH in the majority of newborns is unknown. The aim of this study was to investigate the mutation of thyrotropin receptor (TSHR) gene in Chinese children with congenital hypothyroidism (CH). and the hereditary characteristic.

Methods: Eighteen Chinese children with CH were enrolled for molecular analysis of the TSHR gene and 105 normal controls were evaluated. The exons 1-9, and 10 of TSHR gene were detected by PCR-SSCP (single-stranded conformation polymorphism) and sequenced.

Results: A slower and a faster mobility SSCP shift showed in a 12-year old child with hypoplasic gland. Sequencing of TSHR gene revealed a homozygous mutation (CGC --> CAC, Arg450His) and a polymorphism (GAC --> GAG, Asp727Glu). The controls revealed no variants. The 12 relatives of the proband were enrolled and investigated. Six relatives, including his mother and father, were heterozygous for R450H mutation and D727E polymorphism of the TSHR gene. Thyroid hormone levels were normal except for circulating TSH (5.96-6.92 mU/L) level slightly elevated in six heterozygous family members.

Conclusions: Homozygous mutation R450H of the TSHR gene led to CH. Heterozygous mutation R450H was the cause of subclinical hypothyroidism.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Base Sequence
  • Child
  • Child, Preschool
  • Congenital Hypothyroidism / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Polymorphism, Genetic*
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Thyrotropin / genetics*


  • Receptors, Thyrotropin