DUOX2 and DUOXA2 Variants Confer Susceptibility to Thyroid Dysgenesis and Gland-in-situ With Congenital Hypothyroidism

Congenital and Juvenile Hypothyroidism Due to Thyroid Dysgenesis.

Following the initial description of an ectopic thyroid by Verneuil, ( 1 ) it remained only as an anatomical curiosity for many years. Hunt ( 2 ) described dysphagia and obstruction of the upper larynx caused by a lingual thyroid and suggested the clinical importance of this entity. Mont gomery ( 3 ) has reviewed most of the reported cases, and observed that surgi cal ablation of the ectopic ti...

Compound Heterozygous Mutations in the DUOX2/DUOXA2 Genes Cause Congenital Hypothyroidism

The mutations in the dual oxidase 2 (DUOX2) and dual oxidase maturation factor 2 (DUOXA2) genes can cause congenital hypothyroidism (CH). This study reports the pedigree with goitrous congenital hypothyroidism (GCH) due to the coexistence of heterozygous mutations in the DUOX2 and DUOXA2 genes. The two sisters with GCH were diagnosed with CH at neonatal screening and were enrolled in this study...

Clinical and molecular characteristics of congenital hypothyroidism with DUOX2 mutations

Methods This study included 62 transient or permanent CH patients with normal-sized or enlarged eutopic thyroid. All coding exons of DUOX2 and their intronic flanking sequences were amplified by PCR, and directly sequenced. As for novel sequence variant of DUOX2, functional studies were performed by measuring H2O2 generation in vitro. Clinical presentation was retrospectively reviewed based on ...

Hypothyroidism-associated missense mutation impairs NADPH oxidase activity and intracellular trafficking of Duox2.

In the thyroid gland Duox2-derived H2O2 is essential for thyroid hormone biosynthesis. Several patients were identified with partial or severe iodide organification defects caused by mutation in the gene for Duox2 or its maturation factor, DuoxA2. A Duox2-deficient (Duox2(thyd)) mouse model enabled in vivo investigation of its critical function in thyroid tissues, but its roles proposed in host...

Congenital Hypothyroidism due to Thyroid Dysgenesis: From Epidemiology to Molecular Mechanisms