CHEG
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB42666 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:exploring familial origin of congenital hypothyroidism with eutopic gland
| PRJEB42793 | ENA
Project description:Deficiency in Krüppel-like zinc finger transcription factor, GLI-Similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and by what mechanism GLIS3-dysfunction causes hypothyroidism are unknown. In this study, we demonstrate that GLIS3 acts downstream of thyroid stimulating hormone (TSH)/TSHR and is indispensable for TSH/TSHR-mediated induction of thyroid follicular cell proliferation and thyroid hormone biosynthesis. ChIP-Seq and promoter analysis revealed that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, indicating that these genes are directly regulated by GLIS3. The repression of cell proliferation regulatory genes is due to the inhibition of TSH-mediated activation of the mTORC1/RPS6 pathway as well as direct transcriptional regulation of several cell division-related genes by GLIS3. Consequently, GLIS3-deficiency prevents the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a new and key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells, and uncovers a mechanism by which GLIS3-deficiency causes congenital hypothyroidism and prevents goiter development.
2017-08-30 | GSE103297 | GEO
Project description:We performed a whole-genome DNA methylation analysis (Infinium HumanMethylation450 BeadChip) on peripheral whole blood of 23 twin pairs (10 monozygotic and 13 dizygotic) heterogeneously (4 concordant and 19 discordant) affected by Congenital Hypothyroidism (CH) at birth.
2022-10-03 | GSE161041 | GEO
Project description:Transcriptional profiling of rat liver comparing male rats with congenital hypothyrodism (CH) vs intact at adulhood. Here we studied how CH influences liver gene expression program in adulthood. Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology but its specific influence in liver is less understood. Here we studied how CH influences liver gene expression program in adulthood. Pregnant rats were given anti-thyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as a reduction in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, feed efficiency increased in CH and this was accompanied by significant catch-up growth. On PND80, significant reduction in body mass, tail length, and circulating IGF-I remained in CH rats. On the other hand, mRNA levels of known GH targeted genes were significantly up-regulated. Serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in expression for hepatic genes involved in lipid metabolism with an increased transcription of PPAR and reduced expression of genes involved in fatty acids and cholesterol uptake, cellular sterol efflux, triglycerides assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to hypothyroidism onset in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters, and to T3 replacement with enhanced activation of lipogenic transcriptional program. In summary, we provided in vivo evidence that neonatal hypothyroidism causes long-lasting effects on hepatic transcriptional program and tissue sensitivity to hormone treatment. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. Two conditions CH vs INTACT male rats. Biological replicates: Four independent hybridizations: 4 controls (age-matched intact rats) vs 4 CH (male rats with congenital hypothyroidism) on postnatal day 80 for a total of four arrays. One replicate per array.
2012-03-10 | E-GEOD-32705 | biostudies-arrayexpress
Project description:Congenital Hypothyroidism occurs in 1:3500 live births and is therefore the most common congenital endocrine disorder. A spectrum of defective thyroid morphology, termed thyroid dysgenesis, represents 80% of permanent CH cases. Although several candidate genes have been implicated in thyroid development, comprehensive screens failed to detect mutation carriers in a significant number of patients with non-syndromic TD. Due to the sporadic occurrence of TD, de novo chromosomal rearrangements are conceivably representing one of the molecular mechanisms participating in its aetiology. Recently, the use of array CGH technique has provided the ability to map these variations genomewide with high resolution. We performed an array CGH screen of 74 TD patients to determine the role of copy number variants (CNV) in the aetiology of the disease. We identified novel CNVs in 8.75% of all patients that have not been described as frequent variations in the healthy population. Affected patients presented with athyreosis or thyroid hypoplasia and in one case with associated heart malformation.
2010-06-01 | GSE18152 | GEO
Project description:Screening for chromosomal aberrations by array CGH in 74 patients with congenital hypothyroidism
| PRJNA119487 | ENA
Project description:Whole-exome sequencing of a cohort of families (probands and affected/unaffected relatives) suffering from one of two rare thyroid disorders: congenital hypothyroidism (CH) and resistance to thyroid hormone (RTH).
| EGAS00001001114 | EGA
Project description:The monocarboxylate transporter 8 (Mct8) protein is a primary T4 and T3 (TH) transporter. Mutations of the MCT8-encoding, SLC16A2 gene alters thyroid function and thyroid hormone metabolism, and severely impairs neurodevelopment (Allan-Herndon-Dudley syndrome, AHDS). Mct8-deficient mice manifest thyroid alterations but lack neurological signs. It is thought that Mct8 deficiency in mice is compensated by T4 transport through the Slco1c1-encoded organic anion transporter polypeptide 1c1 (Oatp1c1). This allows local brain generation of sufficient T3 by the Dio2-encoded type 2 deiodinase (D2). The Slc16a2/Slco1c1 (MO) and Slc16a2/Dio2 (MD) double knock out mice lacking T4 and T3 transport, or T3 transport and T4 deiodination, would be more approriate models of AHDS. The goal of this work was to compare the cerebral hypothyroidism of systemic hypothyroidism (SH) caused by thyroid gland blockade with that present in the double KOs.
2020-12-15 | GSE155185 | GEO