The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes

Eur J Endocrinol. 2018 Jun;178(6):623-633. doi: 10.1530/EJE-17-1017. Epub 2018 Apr 12.


Objective: Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited.

Design and methods: One hundred ten patients with primary CH were recruited in this study. All exons and exon-intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees.

Results: Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands.

Conclusions: Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.

MeSH terms

  • Asian People / genetics*
  • China
  • Congenital Hypothyroidism / genetics*
  • Dual Oxidases / genetics
  • Female
  • Forkhead Transcription Factors / genetics
  • Genetic Association Studies
  • High-Throughput Nucleotide Sequencing
  • Homeodomain Proteins / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Iodide Peroxidase / genetics
  • Male
  • Membrane Proteins / genetics
  • Mutation
  • PAX8 Transcription Factor / genetics
  • Pedigree
  • Receptors, Thyrotropin / genetics
  • Sequence Analysis, DNA
  • Thyroglobulin / genetics
  • Thyroid Dysgenesis / genetics
  • Thyroid Nuclear Factor 1 / genetics
  • Transcription Factors / genetics


  • DUOXA2 protein, human
  • FOXE1 protein, human
  • Forkhead Transcription Factors
  • HHEX protein, human
  • Homeodomain Proteins
  • Membrane Proteins
  • NKX2-1 protein, human
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Receptors, Thyrotropin
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Thyroglobulin
  • Dual Oxidases
  • Iodide Peroxidase
  • DUOX2 protein, human