[Molecular genetics of congenital isolated thyrotropin deficiency]

In 1971, the first case of congenital isolated thyrotropin (TSH) deficiency was reported by Miyai et al. Subsequently, the same group reported that the disease was caused by a missense mutation in the CAGYC region of the TSH-beta gene (substitution from G to A in exon 2 which altered the Gly29 [GGA] to Arg29 [AGA]). At present the same mutation was reported in 6 patients in 5 Japanese families. Dacou-Voutetakis reported 3 patients with a nonsense mutation in exon 2 (Glu12 [GAA] to Ter [TAA]) and Rajan reported 3 patients with bioinactive TSH caused by a frameshift mutation in exon 3 (Cys105 [TGT] to Val105 [*GTA] and Val114 [GTA] to Ter [TAG]). Significance of C-X-G-X-C motif for biosynthesis of glycoprotein hormones and mass screening for early diagnosis of this disease were discussed.