Congenital isolated central hypothyroidism: Novel mutations and their functional implications
| Autor: | Eric Fliers, A S Paul van Trotsenburg, Anita Boelen |
|---|---|
| Přispěvatelé: | Laboratory for Endocrinology, Amsterdam Gastroenterology Endocrinology Metabolism, Paediatric Endocrinology, Endocrinology |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
endocrine system endocrine system diseases TBL1X TRH Hypothalamus Hypothyroidism Internal medicine medicine Central hypothyroidism Corepressor Thyroid Macroorchidism business.industry TSH medicine.disease Congenital hypothyroidism IGSF1 Endocrinology medicine.anatomical_structure Pituitary Coactivator Sensorineural hearing loss business Neonatal screening hormones hormone substitutes and hormone antagonists Hormone |
| Zdroj: | Handbook of Clinical Neurology, 180(3rd Series), 161-169 The Human Hypothalamus-Middle and Posterior Region ISBN: 9780128201077 |
| ISSN: | 0072-9752 |
| Popis: | Congenital hypothyroidism is the most frequent endocrine disorder in newborns, occurring in 1 per 3000-4000 newborns. In the Netherlands, the neonatal screening program is based primarily on heel prick thyroxine (T4). In contrast to thyroid-stimulating hormone-based programs, this approach allows for the detection of both primary and central congenital hypothyroidism. Over the past decade, the identification of families with isolated congenital central hypothyroidism enabled the identification of novel genetic causes of this condition, in addition to mutations in the TSHβ-subunit gene and thyrotropin-releasing hormone receptor gene reported earlier. In 2012, loss-of-function mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene, were reported as a genetic cause of a syndrome including X-linked congenital central hypothyroidism and adult macroorchidism. IGSF1 encodes a hypothalamic plasma membrane glycoprotein. Mutations in IGSF1 represent the most prevalent genetic cause of isolated central hypothyroidism to date. In 2016, mutations in the transducin β-like 1X (TBL1X) gene were identified in patients with a combination of mild central hypothyroidism and sensorineural hearing loss. TBL1X is an essential subunit of the NCoR/SMRT corepressor complex and expressed in many tissues including the human hypothalamus and pituitary. In 2018, mutations in the insulin receptor substrate 4 (IRS4) gene were reported in cases of familial isolated central hypothyroidism. IRS4 encodes a hypothalamic protein that is part of the insulin and leptin signaling cascade. These recent developments will broaden our understanding of the role of the hypothalamus in hypothalamus-pituitary-thyroid axis regulation and will help to improve diagnosis and treatment of isolated central hypothyroidism. |
| Databáze: | OpenAIRE |
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