Identification and functional characterization of a novel pax8 mutation (P.his39pro) causing familial thyroid hypoplasia

Megumi Iwahashi-Odano, Yasuko Fujisawa, Tsutomu Ogata, Shinichi Nakashima, Mayumi Muramatsu, Satoshi Narumi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Mutations in PAX8, the gene for a thyroid-specific transcription factor, causes congenital hypothyroidism (CH) with autosomal dominant inheritance. All previously detected PAX8 mutations except one are located in the DNA-binding paired domain. The proband, a 1-yr-old boy, was diagnosed with CH in the frame of newborn screening. He had high serum TSH level (180 mU/L) and low serum free T4 level (0.4 ng/dL). Ultrasonography revealed that the proband had thyroid hypoplasia. Importantly, he had a family history of CH, i.e., his mother also had CH and hypoplasia. Next generation sequencing-based mutation screening revealed a novel heterozygous PAX8 mutation (c.116A>C, p.His39Pro) that was transmitted to the proband from the mother. Expression experiments with HeLa cells confirmed that His39Pro-PAX8 exhibited defective transactivation of the TG promoter–luciferase reporter. In conclusion, we identified and described a novel loss-of-function PAX8 mutation in a family with thyroid hypoplasia. Patients with dominantly inherited CH and no extrathyroidal abnormalities could have PAX8 mutations.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
Journalclinical pediatric endocrinology
Issue number4
Publication statusPublished - 2020 Oct
Externally publishedYes


  • Congenital hypothyroidism
  • Genetics
  • Mutation
  • PAX8

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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