Molecular Analysis of the Thyroid Stimulating Hormone Receptor Gene in Unrelated Patients with Congenital Hypothyroidism

We examined the thyroid stimulating hormone receptor (TSHR) gene in a series of 33 unrelated patients with congenital hypothyroidism (CH). Twelve of the patients had thyroid agenesis, one with thyroid ectopy, 18 with normal thyroid gland and two with unknown status of the thyroid gland. The entire coding region of the TSHR gene (exons 1 to 10) of these patients was PCRamplified and analysed using the single-stranded conformational polymorphism (SSCP) technique. Variations in SSCP banding patterns were detected in seven exons/fragments of the TSHR geneexon 1, exon 6, exon 7, exon 8, exon 9, fragments 3 and 6 of exon 10. Subsequent DNA sequence analysis revealed the presence of eight polymorphisms, two of which were novelIVS5- 31C>T and IVS9+3A>G. The other six polymorphismsIVS6+13A>G, IVS7-25insTCTC, 253C>A (P52T), 561T>C (N187N), 1377G>A (A459A) and 2181C>G (D727E) have all been previously reported. Mutation in the TSHR gene that could be associated with CH phenotypes was not detected in all patients, indicating that the cause of the CH phenotypes was due to mutation in other thyroid-related genes