The C105fs114X is the prevalent thyrotropin beta-subunit gene mutation in Argentinean patients with congenital central hypothyroidism.

BACKGROUND Congenital isolated thyrotropin (TSH) deficiency is an unusual condition characterized by low levels of thyroid hormones and TSH, usually presenting early typical signs of severe hypothyroidism. Five different beta-TSH mutations have been described so far. While 4 of them affect only consanguineous families, a frameshift mutation in exon 3 (C105fs114X) has been found also in nonconsanguineous families. OBJECTIVE The aim of the present study was to characterize beta-TSH mutations in Argentinean patients with congenital central hypothyroidism (CCH) and to emphasize the importance of early biochemical and molecular diagnosis of this disorder. PATIENTS AND METHODS We investigated 8 Argentinean children (3 boys, 5 girls) from 7 unrelated families with CCH based upon low levels of T(4) and T(3), and low basal and stimulated TSH levels. Mutation characterizations for the beta-TSH gene were performed by PCR amplification followed by sequence and restriction enzyme analysis with SNABI in the patients, 9 parents and in 100 newborn children. RESULTS All patients presented the same homozygous mutation in exon 3 of the beta-TSH gene (C105fs114X), the 9 studied parents were heterozygous for the same mutation and 1 carrier was found in the 100 studied newborns. CONCLUSION Our findings show that the C105fs114X mutation is prevalent in our population and may constitute a hot spot at codon 105 in the beta-TSH gene. Since this mutation is easily demonstrable by a SNABI digestion in DNA amplified from dried blood spots, its investigation would be indicated in patients in our milieu with clinical and biochemical features of CCH, allowing early L-thyroxine (LT(4)) replacement and genetic counseling of the family.