TOTAL IODIDE ORGANIFICA TION DEFECT (TIOD) IN PATIENTS WITH CONGENITAL HYPOTHYROIDISM (CH): MUTATlON OF THE DUAL OXIDASE 2 (DUOX2) GENE

GRUNEIRO-PAPENDIECK, LAURA; CHIESA, ANA; VARELA, VIVIANA; RIVOLTA, CARINA; TARGOVNIK, HÉCTOR

Angra dos Reis, Brasil

Congreso; XVII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica; 2004

Sociedad Latinoamericana de Endocrinología Pediátrica

Introduction: Congenital hypothyroidism (CH) is a prevalent disease affecting about 1:3000 newborns. Thyroid dysgenesis is responsible for 80-85% of this disorder while a eutopic gland is present in the other 10-15%. In these patients, thyroid insufficiency may be caused by defects in iodine organification due to defects of the thyroid peroxidase (TPO) and less frequently in dual oxidase 1 (DUOX1) and 2 (DUOX2), components of the peroxide generating system. Aim: To identify DUOX2 gene mutations in patients with congenital goiter and CH, clinically and biochemically selected. Patients and Methods: We studied 14 patients with CH and goiter, most detected by newbom CH screening. AII selected patients showed at diagnosis or reevaluation high TSH levels, low T4, elevated thyroglobulin values and perchlorate discharge test >50%. In 6 patients mutations of the TPO gene were found, 4 carried two different heterozygous mutations, and 2 were simply heterozygous (previously reported). In the 8 remaining patients and in those with only one affected allele for TPO mutations, DNA coding sequences and their flanking regions of exons 12, 13, 16, 17, 20 and 22 of the DUOX2 gene were analysed by SSCP and DNA sequencing. Results: One mutation of the DUOX2 gene was found in two affected siblings of a non¡©consanguineous family. Genomic DNA sequencing revealed both patients were hetero¡©zygous for a single base change of an adenine to cytosine transversion at position -2 of the splice acceptor site in intron 19 (2840-2 A¡æC) which modifies the acceptor splice consensus sequence. The father´s and two healthy brothers´ DNA showed this heterozygous mutation in intron 19. 100 chromosomes from the general population were analysed with SSCP. Conclusions: To our knowledge, this is the first report of an affected family with DUOX2 disorder in our country. This finding confirms the recessive inheritance ofthe disease. This disorder should be excluded in patienls with TIOD.