Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2.

Here, we describe three cases of loss-of-function mutations in the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (NOX) domain of dual oxidase 2 (DUOX2) occurring along with concurrent missense mutations in thyroid peroxidase (TPO), leading to transient congenital hypothyroidism (CH). Three Japanese boys with nonconsanguineous parents were diagnosed with CH during their neonatal screenings. All patients presented with moderate-to-severe neonatal hypothyroidism and were diagnosed with transient CH after re-evaluation of thyroid function.

Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene.

Subjects who are heterozygous for thyroid stimulating hormone receptor (TSHR) gene mutations present various phenotypes that range from euthyroid to hyperthyrotropinemia. Similarly, heterozygous dual oxidase 2 (DUOX2) gene mutations result in variable phenotypes, such as transient congenital hypothyroidism, subclinical hyperthyrotropinemia, and euthyroid in children. Here, we describe an 8-year-old boy who had normal newborn screening results, but who developed nonautoimmune hypothyroidism at the age of 1 year and 8 months of age.

Congenital hypothyroidism caused by a novel mutation of the dual oxidase 2 (DUOX2) gene.

The dual oxidase 2 (DUOX2) mutation results in an impairment of the hydrogen peroxidase-generating system and is identified as a dyshormonogenic cause of congenital hypothyroidism (CH). Here, we describe two unrelated Japanese girls with CH due to a novel DUOX2 mutation. They had high serum thyrotropin levels and low free thyroxine/thyroxine concentrations during the neonatal period.

Genetic analysis in children with transient thyroid dysfunction or subclinical hypothyroidism detected on neonatal screening.

About 30% of children with elevated TSH levels during neonatal screening have a transient form of disorder. On the other hand, it has been reported that subclinical hypothyroidism persists in late childhood in about 30% of children found to be false-positive during neonatal screening. The aim of this study was to determine whether transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening are influenced by genetic background.

Correlation between clinical phenotypes and X-inactivation patterns in six female carriers with heterozygote vasopressin type 2 receptor gene mutations.

About 90% of patients with congenital nephrogenic diabetes insipidus (NDI) have vasopressin type 2 receptor (V2R) gene mutations that are inherited in an X-linked recessive manner. Although most female carriers are asymptomatic, some female carriers show polydipsia and polyuria. The reason why female carriers show NDI symptoms is explained by skewed X-inactivation.

IGF binding protein-5 synthesis is regulated by testosterone through transcriptional mechanisms in androgen responsive cells.

We found that androgen and IGF-I up-regulated IGFBP-5 mRNA in androgen-responsive normal human fibroblast, which was blocked by co-treatment with 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole, but not cycloheximide. IGFBP-5 promoter activity was stimulated by androgen. Nuclear run-on assay revealed that IGFBP-5 transcripts were increased in response to androgen, which was not enhanced by co-addition of IGF-I.