ESPE Abstracts

Background: The morphological and biochemical phenotype of Paired Box Domain Gene PAX8 mutation in patients with congenital hypothyroidism (CH) is variable. The contribution of mutations in PAX8 gene in children with CH and dysgenetic or orthotopic thyroid glands still remains a subject of interest of researchers.

Objective and hypotheses: This study presents mutational analysis of the PAX8 gene in patients with primary CH.

Method: 50 children (36 girls, 14 boys) with CH connected with thyroid ectopy (n=18), aplasia (n=10), hypoplasia (n=2), thyroid dysgenesis of unknown reason (n=13) or orthotopic thyroid (n=7) were enrolled. Study participants were born in south-eastern Poland in years 1993–2012 and selected in neonatal mass screening for CH. DNA was extracted from peripheral blood samples with the use of Master Pure DNA Purification Kit (Epicentre Biotechnologies). The 12 exons of the PAX8 gene along with their exon–intron boundaries were amplified and sequenced by Sanger method. Capillary electrophoresis was run on ABI 3500 (Applied Biosystems).

Results: Two heterozygous transitions in exon 3 (c.68G>A) and in exon 5 (c.404A>G) were detected in a 3-year-old girl with a thyroid hypoplasia. One heterozygous transition in exon 5 (c.404A>G) was found in a 15-year-old girl with a thyroid aplasia. Additionally, a novel genetic variant in 3′UTR region of exon 12 (c.1971C>T) occurred in a 3-year-old boy with ectopic thyroid tissue. Well-described SNPs in exon 12 were revealed in 48 children.

Conclusion: The study reports the occurrence of two novel missense substitutions in the PAX8 gene and also confirms a very low prevalence of PAX8 mutations in thyroid dysgenesis. Estimation of the contribution of the revealed mutation to the etiology of CH in two girls with hypoplastic and aplastic thyroid requires further functional analysis.