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

Mutations in , the gene for a thyroid-specific transcription factor, causes congenital hypothyroidism (CH) with autosomal dominant inheritance. All previously detected 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 T level (0.4 ng/dL). Ultrasonography revealed that the proband had thyroid hypoplasia. Importantly, he had a family history of CH, , his mother also had CH and hypoplasia. Next generation sequencing-based mutation screening revealed a novel heterozygous 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 promoter-luciferase reporter. In conclusion, we identified and described a novel loss-of-function mutation in a family with thyroid hypoplasia. Patients with dominantly inherited CH and no extrathyroidal abnormalities could have mutations.