Identification and functional characterization of a novel PAX8 mutation (p.His39Pro) causing familial thyroid hypoplasia.

Abstract

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.

• Authors: Megumi Iwahashi-Odano, Yasuko Fujisawa, Tsutomu Ogata, Shinichi Nakashima, Mayumi Muramatsu, Satoshi Narumi
• Journal: Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology (Clin Pediatr Endocrinol) Vol. 29 Issue 4 Pg. 173-178 ( 2020) ISSN: 0918-5739 [Print] Japan
• PMID: 33088016 (Publication Type: Journal Article)
• Copyright: 2020©The Japanese Society for Pediatric Endocrinology.