This dyshormonogenesis displays a wide phenotype variation and is characterized usually by: the presence of congenital goiter or goiter appearing shortly after birth, high (131)I uptake, negative perchlorate discharge test, low serum TG and elevated serum TSH with simultaneous low serum T(4) and low, normal or high serum T(3).
Our findings confirm the genetic heterogeneity of TPO defects and the importance of the implementation of molecular studies to determinate the aetiology of the CH with dyshormonogenesis.
Based on clinical and pathophysiological parameters, the cause of the thyroid dyshormonogenesis was suspected to be a defect in the synthesis of thyroglobulin, the matrix protein for thyroid hormone synthesis in the thyroid gland.
The variants in 'dyshormonogenesis' (DH) genes were found in 84.8% (78/92) of cases: TPO, n = 30; DUOX2, n = 24; TG, n = 8; SLC5A5, n = 3; SLC26A4, n = 6; IYD, n = 1.8 patients showed oligonenic variants.
A defect in thyroid peroxidase is a common cause of dyshormonogenesis of the thyroid gland in Taiwanese, with a novel mutation (2268insT) present in nearly 90% of alleles studied.
The occurrence of thyroid carcinoma in patients with congenital hypothyroidism (CH) caused by dyshormonogenesis is very rare, and has only been reported in one patient harboring mutations in the thyroid peroxidase (TPO) gene.
The present Review reports data on the prevalence of DUOX2 mutations, which is variable among different series but invariably high, pointing to DUOX2 defects as one of the leading causes of dyshormonogenesis.
However, in populations where resources for screening and detection are limited, and especially where consanguineous marriages are common, mutations in genes involved in thyroid function may also be causes of ID, and as TPO and TG mutations are the most common genetic causes of TDH, these are also likely to be relatively common causes of ID.