Monogenic Thyroid Disorder

Sun Wook Cho; Young Joo Park

doi:10.11106/jkta.2012.5.2.83

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Cho and Park: Monogenic Thyroid Disorder

Review Article

Journal of Korean Thyroid Association

Journal of Korean Thyroid Association 2012; 5(2): 83-93.

Published online: 28 November 2012

DOI: https://doi.org/10.11106/jkta.2012.5.2.83

Monogenic Thyroid Disorder

Sun Wook Cho, Young Joo Park

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Correspondence: Young Joo Park, MD, PhD, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. Tel: 82-2-2072-4183, Fax: 82-2-762-2292, yjparkmd@snu.ac.kr

Received 26 April 2012 Accepted 25 June 2012

(open-access):

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Monogenic disorder is a single gene disorder resulted of a single mutated gene. Monogenic disorder has benefits in early diagnosis and precious prediction of disease course. Furthermore, monogenic disorder could provide an informative knowledge to the understanding of related pathophysiology. Thyroid monogenic disorder could occur in various steps, such as thyroid development, hormonogenesis, TSH-receptor signaling, thyroid hormone transport and end organ response. Here, we reviewed of congenital hypothyroidism, congenital hyperthyroidism and thyroid hormone resistance syndrome.

Keywords: Monogenic disorder, Congenital hypothyroidism, Congenital hyperthyroidism, Thyroid hormone resistance syndrome

Figures and Tables

Fig. 1

Monogenic disorders of thyroid disease. Genes associated with thyroid gland development, thyroid hormone synthesis, transport, action through TSH receptor or central regulation by Hypothalamus-Pituitary-Thyroid axis could be a cause of monogenic thyroid disease.

Fig. 2

Molecular genetic approaches of congenital hypothyroidism (CH).11) PDT: perchlorate discharge test, PIOD: partial iodide organification defect (PDT<90%), TIOD: total iodide organification defect (PDT>90%), NKX2.1: also known as TTF-1, TITF1, or T/EBP, FOXE1: also known as TTF-2, TITF2 or FKHL15, PAX-8: paired box transcription factor 8, TSH: thyrotropin, TSHR: receptor for TSH, NIS: sodium iodide symporter, SLC26A4: gene encoding pendrin (also known as PDS, Pendred syndrome), a multifunctional anion exchanger, DEHAL1: iodotyrosine deiodinase, TG: thyroglobulin, TPO: thyroperoxidase, DUOX2: dual oxidase 2, DUOXA2: dual oxidase maturation factor A2.

Fig. 3

Clinical characteristics of thyroid hormone resistance syndrome (RTH). Generalized thyroid receptor (TR) β mutation tends to show mental retardation with no definite abnormality of thyroid hormonal function. When the effects of TR β mutation is dominant in pituitary rather than peripheral tissues, patients show clinical hyperthyroidism. On the contrary, the effects of TR β mutation is dominant in peripheral tissues rather than pituitary, hypothyroidism is the main clinical manifestations.

Fig. 4

Pathophysiology of congenital hypothyroidism. Congenital hypothyroidism shows diverse phenotypes according to the strength of thyroid stimulating hormone receptor (THSR), number of affected cells, and disease onset.37)

Table 1

Classification of monogenic disorders in hypothalamus-pituitary-thyroid axis

Table 2

Diagnosis of thyroid hormone resistance syndrome

GRTH: generalized resistance to thyroid hormone, PRTH: pituitary resistance to thyroid hormone

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