The objective of this study is to analyze the recurrence of the p.R277X/p.R1511X compound heterozygous mutation in the TG gene in two unrelated families (one Argentinian and another Brazilian) with congenital hypothyroidism, goiter and impairment of TG synthesis.
167 different mutations, many of which are newly discovered, are now known to exist in TG (encoding human thyroglobulin) that can lead to defective thyroid hormone synthesis, resulting in congenital hypothyroidism.
We report on a German girl with congenital hypothyroidism due to a mutation in the thyroid peroxidase (TPO) gene who had elevated serum levels of thyroglobulin during periods of hyperthyrotropinemia.
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).
Inherited as an autosomal recessive trait, deficient Tg causes congenital hypothyroidism in newborns that, if untreated, results in goiter along with serious cognitive and growth defects.
Clinical case seminar: metastatic follicular thyroid carcinoma arising from congenital goiter as a result of a novel splice donor site mutation in the thyroglobulin gene.
Of note, blood thyroglobulin was unexpectedly elevated in the patients at the time of diagnosis, a finding that might prove useful in refining etiologies of congenital hypothyroidism.
Evidence for the segregation of three different mutated alleles of the thyroglobulin gene in a Brazilian family with congenital goiter and hypothyroidism.
Our study provides further evidence that mutations in the TG gene cause congenital goiter and hypothyroidism, demonstrates genetic heterogeneity of the mutation, and increases our understanding of phenotype-genotype correlations in congenital hypothyroidism.
A combination of nonsense mutations, frameshift mutations, splice site mutations, and missense mutations in Tg occurs spontaneously to cause congenital hypothyroidism and thyroidal ER stress.