CONGENITAL HYPOTHYROID GOITER WITH DEFICIENT THYROGLOBULIN (TG) SYNTHESIS: PRELIMINARY MOLECULAR APPROACH

CHIESA A,; RIVOLTA C,; CAPUTO M,; TARGOVNIK H,; GRUÑEIRO- PAPENDIECK L

Viña del Mar Chile

Congreso; XVIII Reunion Anual de la Sociedad Latinoamericana de Endocrinologia Pediatrica; 2006

SLEP

Congenital hypothyroidism (CH) may be due to defects in thyroid development (75%) and dishormonogenesis (25%) . Among the latter, defects of TPO, DUOX2, pendrin originate iodine organification defects and mutations of TG gene originate defective TG. We report the evaluation  of  patients with CH,  goitre and TG defect synthesis. Patients and methods: We studied 11/50 CH with goitre detected mostly by newborn screening, selected if they had at diagnosis or reevaluation high TSH levels, low T4 and TG values. 8 underwent a perchlorate discharge test that was always  negative (<10%). 22 of 48 exons of the TG gene were studied by DNA sequencing. Results We found mutations in 7/11 patients 1)Two hypothyroid siblings from non consanguineous parents were compound heterozygous for a 886C>T in exon 7 and a 4588C>T in exon 22,  substitutions that resulted in a premature stop codon at aminoacids 277 (R277X) and 1511 (R1511X) respectively.2)One patient was homozygous R277X mutation in exon 7. 3)Three patients were heterozygous R277X in exon 7 4)One patient had an heterozygous insertion in exon 7 Conclusion Low TG levels in a goitrous hypothyroid patient suggest a Tg synthesis defect. 7/11 patients with  these features showed  mutations in exon 7 , 2 as compound heterozygous, 1 homozygous and 4 heterozygous with only 1 mutation found. Coinciding with previous reports the R277X mutation was the most frequently found and could be considered as a hot spot. Consequently, it would be helpful to consider its investigation in patients with defective TG synthesis