Abstract

Hereditary hypothyroidism caused by thyroid-stimulating hormone (TSH) deficiency is a rare autosomal recessive disease. Affected individuals show symptoms of severe mental and growth retardation that can be prevented by early administration of exogenous thyroid hormone. In this paper, we describe two related Greek families with three children affected by congenital TSH-deficient hypothyroidism. Sequence analysis of the TSH beta-subunit gene (TSHB) showed that the mutation responsible for the hypothyroidism in these families is a nonsense mutation in exon 2. This mutation is a G-to-T transversion at nucleotide 94 that destroys the only TaqI site in the TSHB-coding region and gives rise to a novel 8.5-kb TaqI fragment. Restriction analysis showed that the three affected children are homozygous for the 8.5-kb allele and that the four parents and two unaffected children are heterozygous. This mutation gives rise to a truncated peptide which includes only the first 11 of 118 amino acids of the mature TSHB peptide.