This is the first time that a loss of function mutation of the TSH receptor is described in a patient with severe congenital hypothyroidism and absent circulating thyroglobulin due to TSH unresponsiveness and the first time that an inactivating mutation of the TSH receptor is described in the first extracellular loop.
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.
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.
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.
Qualitative and quantitative defects of thyroglobulin resulting in congenital goiter. Absence of gross gene deletion of coding sequences in the TG gene structure.
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.
Thyroid scans, serum thyroglobulin measurements, and free T4 measurements using equilibrium dialysis or 2-step immunoassay methods can identify thyroid hormone-binding protein defects and simplify the diagnosis and treatment of infants with CH.
A nonsense mutation causes human hereditary congenital goiter with preferential production of a 171-nucleotide-deleted thyroglobulin ribonucleic acid messenger.