Structure and genetic variants of thyroglobulin: Pathophysiological implications
| Autor: | Carina M. Rivolta, Héctor M. Targovnik, Cintia E. Citterio |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Models Molecular Thyroid Hormones Protein Conformation medicine.medical_treatment 030209 endocrinology & metabolism Disease Biology Bioinformatics Biochemistry Thyroglobulin 03 medical and health sciences 0302 clinical medicine Endocrinology Thyroid dyshormonogenesis medicine Congenital Hypothyroidism Animals Humans Molecular Biology Gene Thyroid Genetic Variation Oligogenic Inheritance medicine.disease Pathophysiology Congenital hypothyroidism 030104 developmental biology medicine.anatomical_structure |
| Zdroj: | Molecular and cellular endocrinology. 528 |
| ISSN: | 1872-8057 |
| Popis: | Thyroglobulin (TG) plays a main role in the biosynthesis of thyroid hormones (TH), and, thus, it is involved in a wide range of vital functions throughout the life cycle of all vertebrates. Deficiency of TH production due to TG genetic variants causes congenital hypothyroidism (CH), with devastating consequences such as intellectual disability and impaired growth if untreated. To this day, 229 variations in the human TG gene have been identified while the 3D structure of TG has recently appeared. Although TG deficiency is thought to be of autosomal recessive inheritance, the introduction of massive sequencing platforms led to the identification of a variety of monoallelic TG variants (combined with mutations in other thyroid gene products) opening new questions regarding the possibility of oligogenic inheritance of the disease. In this review we discuss remarkable advances in the understanding of the TG architecture and the pathophysiology of CH associated with TG defects, providing new insights for the management of congenital disorders as well as counseling benefits for families with a history of TG abnormalities. Moreover, we summarize relevant aspects of TH synthesis within TG and offer an updated analysis of animal and cellular models of TG deficiency for pathophysiological studies of thyroid dyshormonogenesis while highlighting perspectives for new investigations. All in all, even though there has been sustained progress in understanding the role of TG in thyroid pathophysiology during the past 50 years, functional characterization of TG variants remains an important area of study for future advancement in the field. |
| Databáze: | OpenAIRE |
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