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 present a patient with congenital hypothyroidism (CH) who presented in newborn screening with elevated serum thyroid-stimulating hormone (TSH), decreased free thyroxine (fT4) and increased thyroglobulin (Tg) concentrations.
The ChEL domain is critical for protein folding and patients with CH due to misfolded TG may present without low serum TG despite the TG gene mutations.
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.
The aim of the present study was to identify new TG mutations in a patient of Vietnamese origin affected by congenital hypothyroidism, goiter and low levels of serum TG.
The aim of this study was to perform the genetic analysis of the TG gene in two sisters born from consanguineus parents and affected by CH and low serum TG levels.
For example, misfolding of insulin can result in autosomal dominant mutant INS gene-induced diabetes of youth, and misfolding of thyroglobulin can result in autosomal recessive congenital hypothyroidism with deficient thyroglobulin.
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.
Further diagnostic approaches, such as ultrasonography, scintigraphy and measurement of thyroglobulin levels, to determine the subtype of congenital hypothyroidism, should not delay initiation of treatment.
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).
By incorporating the R451C mutation found in neuroligin (NLGN) and associated with autism and the thyroglobulinG2320R (G221R in NLGN) mutation responsible for congenital hypothyroidism into NLGN3, we show that mutations in the alpha/beta-hydrolase fold domain influence folding and biosynthetic processing of neuroligin3 as determined by in vitro susceptibility to proteases, glycosylation processing, turnover, and processing rates.
To reveal new aspects of thyroglobulin pathophysiology through clinical, cellular, molecular, and genetic studies in a family presenting with CH due to TG mutations from Galicia, an iodine-deficient area of Spain.
We describe the clinical, biochemical, and molecular findings of a cohort of Argentinean patients with congenital hypothyroidism (CH) and goiter studied to characterize iodide organification and thyroglobulin (TG) defects.
The aim of the study was to report the genetic screening of 15 patients with CH due to TG gene mutations and to perform functional analysis of the p.A2215D mutation.