Background: Heterozygosity of genetically encoded misfolded mutant thyroglobulin (TG, the thyroid hormone protein precursor) occurs with a frequency estimated at 1-in-217 people worldwide, resulting in subclinical hypothyroidism that largely escapes medical detection. However, patients carrying biallelic TG mutation, when untreated, are frankly hypothyroid unless and until they develop a massive goiter. To date, TG is the only proven endogenous precursor protein for thyroid hormone synthesis in vertebrates.
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