Our objective was to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD, and TSHR) in CH cases with GIS.
Three mutations (p.Q36H, p.G418fsX482, and g.IVS19-2A>C) in the dual oxidase 2 gene responsible for congenital goiter and iodide organification defect.
Only one study reported mutations in DUOX2 gene in congenital hypothyroidism (CH) associated with total iodide organification defect (TIOD) in homozygosity or with partial iodide organification defect (PIOD) in heterozygous patients.
The objective of this study was to screen and subsequently identify TPO gene mutations in patients with congenital hypothyroidism with evidence of total iodine organification defects (TIOD) or partial iodine organification defect (PIOD) as defined by the perchlorate discharge test.
Homozygous loss-of-function mutations in the FOXE1 gene have been reported in several patients with partial or complete Bamforth-Lazarus syndrome: congenital hypothyroidism (CH) with thyroid dysgenesis (usually athyreosis), cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis.
Therefore, the unfavorable outcome in patients with CH, especially those with choreoathetosis and pulmonary symptoms, can be explained by mutations in the NKX2-1 gene rather than by hypothyroidism.