Genetic analysis of the PAX8 gene in children with congenital hypothyroidism and dysgenetic or eutopic thyroid glands: identification of a novel sequence variant
| العنوان: | Genetic analysis of the PAX8 gene in children with congenital hypothyroidism and dysgenetic or eutopic thyroid glands: identification of a novel sequence variant |
|---|---|
| المؤلفون: | Ferruccio Santini, Patrizia Agretti, Luca Chiovato, Anna Perri, Paolo Vitti, Giuseppina De Marco, E. Ferrarini, Lucia Montanelli, Aldo Pinchera, Caterina Di Cosmo, Arash Ordookhani, Maria Elena Banco, Massimo Tonacchera |
| المصدر: | Clinical Endocrinology. 67:34-40 |
| بيانات النشر: | Wiley, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Adult, Male, endocrine system, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, DNA Mutational Analysis, Thyroid Transcription Factor 1, Thyroid Gland, Thyroid Function Tests, Biology, Transfection, Thyroglobulin, Thyroid function tests, Cell Line, PAX8 Transcription Factor, Endocrinology, Hypothyroidism, Internal medicine, Congenital Hypothyroidism, medicine, Humans, Paired Box Transcription Factors, Euthyroid, Child, Luciferases, Promoter Regions, Genetic, medicine.diagnostic_test, Thyroid, Infant, Newborn, medicine.disease, Congenital hypothyroidism, DNA-Binding Proteins, Enzyme Activation, medicine.anatomical_structure, Mutagenesis, Site-Directed, Female, PAX8, HeLa Cells, Transcription Factors, Endocrine gland |
| الوصف: | Summary Objective To analyse the coding region of PAX8 in individuals with congenital (CH) or post neonatal hypothyroidism due to dysgenetic (TD) or eutopic thyroid glands. Design and patients Forty-three children with CH and TD (13 agenesis, 23 ectopia, and seven hypoplasia), one subject with post neonatal onset of hypothyroidism and thyroid ectopia, 15 children with CH and eutopic thyroid glands and six euthyroid adults with thyroid hemiagenesis were enrolled as cases, along with 120 healthy individuals as controls. Measurements Exons 2–8 of the PAX8 were directly sequenced. HeLa and HEK293 cells were transfected with PAX8 wild-type (PAX8-WT), mutant PAX8, p300, thyroid transcription factor 1 (TTF-1) and thyroglobulin promoter pGL3 (TG prom-pGL3). Synergism of TTF-1 with PAX8-WT vs. mutant and activity of PAX8-WT vs. mutant in accompaniment with p300 on TG prom-pGL3 were also assessed. The luminescence produced by PAX8-WT and mutant PAX8 was measured. Results Among patients and controls only a 15-year-old girl with thyroid ectopia showed a heterozygous transition of cytosine to thymine at position 674 in exon 6, which changed a conserved threonine at position 225 to methionine (PAX8-T225M). Her father and sister harboured PAX8-T225M without abnormal thyroid phenotypes. PAX8-T225M and PAX8-WT similarly increased luciferase activity and had a similar synergistic effect with TTF-1. At 500 ng p300, however, PAX8-T225M could not significantly increase TG promoter activity when compared to PAX8-T225M alone, while PAX8-WT +500 ng p300 induction was significantly higher than PAX8-WT alone (P |
| تدمد: | 1365-2265 0300-0664 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ad6c92ea19f434b02502629e774e039Test https://doi.org/10.1111/j.1365-2265.2007.02831.xTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....2ad6c92ea19f434b02502629e774e039 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652265 03000664 |
|---|