Mutation of a Gene for Thyroid Transcription Factor-1 (TITF1) in a Patient with Clinical Features of Resistance to Thyrotropin

Endocrine Journal

Makoto UCHIYAMA¹  Tomonobu HASEGAWA²  Tadashi ASAMI³  Toru KIKUCHI¹  Keisuke NAGASAKI¹  Satoshi NARUMI² 

[1] Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medicine and Dental Sciences;Department of Pediatrics, Keio University School of Medicine;Faculty of Nursing, Social Welfare, and Psychology, Department of Nursing, Niigata Seiryo University

关键词: TITF1;    Congenital hypothyroidism;    Resistance to TSH;   

DOI  :  10.1507/endocrj.K08E-124

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(15)Cited-By(7)Resistance to TSH (RTSH [MIM 275200]) is a heterogeneous condition defined by variable degree of insensitivity to biologically active TSH. While this condition is classically caused by loss-of-function mutations of the TSH receptor gene (TSHR), several patients have exhibited RTSH-like phenotype in the apparent absence of TSHR mutations, and some of them have mutations of PAX8 or GNAS1. We identified a Japanese boy with congenital hypothyroidism who suffered from recurrent lower respiratory infection during infancy and choreoathetosis at a later age. At 14 years of age, he was diagnosed as having RTSH, on the basis of compensated hypothyroidism (TSH, 30.2 mU/L; FT4, 1.2 ng/dl), disproportionate increments of thyroid hormones and TSH during a TRH test (ΔFT3, 0.4 pg/ml; ΔT3, 13 ng/dl; and ΔTSH, 88.3 mU/L), and normal ultrasound thyroid image and radioactive iodine uptakes. Molecular analysis for TITF1 revealed a novel de novo heterozygous deletion/insertion mutation (c.470_479delinsGCG,) that is predicted to lose the entire homeodomain and the NK2-specific domain. We suggest that a heterozygous loss-of-function TITF1 mutation can also cause RTSH-compatible phenotype.

【 授权许可】

Unknown