TG Gene Mutations and Congenital Hypothyroidism
TG Gene Mutations and Congenital Hypothyroidism
The aim of this study was to identify mutations in the thyroglobulin gene that might be
 present in patients with fetal goiter and congenital goiter hypothyroidism.
Congenital goitrous hypothyroid is commonly linked to thyroglobulin (TG) gene mutations.We
 aim to identify mutations in the TG gene that might be present in patients with fetal goiter
 and congenital goiter hypothyroidism.Four related patients with congenital goiter
 hypothyroidism from an inbred family were studied.Recombinant human TSH stimulation test, DNA
 sequencing and protein computer analysis were performed.We identified a novel compound
 heterozygous constellation (IVS30+1G>T/A2215D) in two siblings. It was also identified a
 homozygous intronic mutation (IVS30+1G>T) in their cousins, one of them with fetal goiter.
 The mutation IVS30+1G>T promotes an aberrant splicing and loss of the entire exon 30 (138 nt)
 in the resulting messenger RNA. The recent described mutation A2215D is located in the
 ACHE-like domain, which functions as a dimerization domain, facilitating efficient
 intracellular transport of the protein. Protein computer analysis suggested that the A2215D
 mutation causes TG structural alterations.A novel compound heterozygous constellation
 (IVS30+1G>T/A2215D) and the previously described mutation (IVS30+1G>T) that cause severe
 congenital hypothyroidism due to defective TG synthesis have been identified. The mutation
 IVS30+1G>T may be related to fetal goiter and hypothyroidism due to TG instability and
 impaired TG export to the colloid. This study shows the efficiency of the use of rhTSH in the
 differential diagnosis of CH due to TG defective synthesis and the importance of molecular
 diagnosis of CH for possible intrauterine treatment, thereby avoiding damage to the
 neuropsychomotor system.
Inclusion Criteria:

 -  Patients with congenital hypothyroidism due to thyroglobulin defective synthesis.

 Exclusion Criteria:

 -  Patients with another disease.