A new familiar case of congenital goiter with hypothyroidism caused by homozygous mutation in the thyroglobulin gene

PELLIZAS CG; SOBRERO G; BOYANOSKI A; NIEVA V; TESTA G; BAZZARA LG; DIPOI M; MACHIAVELLI G; RIVOLTA C; TARGOVNIK HM; MIRAS MB

Mar del Plata, Bs As, Argentina

Congreso; XIX Congress of the Latin American pediatric Society; 2007

Latin American Pediatric Society

The prevalence of Congenital Hypothyroidism (CH) in Cordoba city is 1/2185 newborns. Eutopic thyroid glands were seen in 41% of these patients. In order to ascertain a dishormonogenesis in 5 unrelated patients with a marked impairment of thyroglobulin (TG) levels, goitrous thyroid glands with increased radioisotopic uptake, serum thyrotropin augmented and low thyroid hormone levels, genomic DNA was analyzed with the aim of search for a TG synthesis defect. DNA sequencing from one of the studied patients revealed an homozygous mutation in exon 7 (c.886C�¨T) determining a premature stop codon at amino acid 277 (p.R277X) that results in a grossly truncated protein of only 276 amino acids with marked reduction in the ability to generate thyroid hormone. Two other brothers of this patient, previously diagnosed with CH, exhibited the same mutation, one of them with a severe mental retardation as a consequence of a late diagnosis. The same mutation was previously identified in brazilian and argentinean families. To conclude, we report here a new case of congenital goitrous hypothyroidism, in an Argentinean family, that is homozygous for the p.R277X mutation. The present study suggests that this TG mutation gene is a mutational  hot spot.