Endocrine Abstracts

Background: Dyshormonogenetic goiter and Hashimoto’s thyroiditis are amongst the commonest causes of hypothyroidism in children and adolescents Worldwide. But, the genetic basis and their hypothyroid phenotypes are under-reported, especially from developing countries. In this context, we screened for dyshormonogenetic mutations in hypothyroid children with dyshormogenetic goiter (DH) and Hashimoto’s thyroiditis (HT).

Material and methods: In this prospective multidisciplinary study, blood DNA of 42 hypothyroid children with dyshormogenetic goiter (DH) and Hashimoto’s thyroiditis (HT) were studied with direct sequencing analysis for NIS, DUOX2 and TPO gene mutations. Detailed clinical, biochemical and follow-up data were analysed.

Results: Mean age of children was 11.35±2.03 years (5–18). In the entire cohort, we detected 17/42 (40.4%) thyroid specific mutations. In HT, we detected eight mutations in 7/20 (35%) children of this cohort (six in NIS and two in Tpo genes). In DH, nine mutations in 8/22 (36%) children were detected. No mutations were observed in Duox2 gene. All our mutations were localized in introns. Except for two homozygous polymorphisms, all other mutations were heterozygous in nature. Genotype-phenotype correlations shows statistically significant expression of autoimmune manifestations, goiter rate and positive family history.

Conclusions: NIS gene mutations were the most prevalent mutations in both HT and DH amongst South Indian children in this study. These mutations significantly influenced hypothyroid phenotypic traits such as severity of hypothyroidism, goiter rate, autoimmune associations and positive family history. More studies from varied geographic zones are needed to risk categorise hypothyroid phenotypes in children.