通常, TSH 纯合子突变可导致先天性中枢性甲状腺功能减退症以及家族聚集现象。但是,编码 TRH 受体、TSH β亚基和免疫球蛋白超家族因子 1 (IGSF1) 的垂体选择性基因与孤立的中枢性甲状腺功能减退症相关。[18]Tajima T, Nakamura A, Ishizu K. A novel mutation of IGSF1 in a Japanese patient of congenital central hypothyroidism without macroorchidism [Rapid Communication]. Endocr J. 2013;60:245-249.https://www.jstage.jst.go.jp/article/endocrj/60/2/60_EJ13-0009/_pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23363888?tool=bestpractice.com[19]García M, Fernández A, Moreno JC. Central hypothyroidism in children. Endocr Dev. 2014;26:79-107.http://www.ncbi.nlm.nih.gov/pubmed/25231446?tool=bestpractice.com[20]Tajima T, Nakamura A, Morikawa S, et al. Neonatal screening and a new cause of congenital central hypothyroidism. Ann Pediatr Endocrinol Metab. 2014;19:117-121.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208260/http://www.ncbi.nlm.nih.gov/pubmed/25346914?tool=bestpractice.com[22]Persani L, Bonomi M. The multiple genetic causes of central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2017;31:255-263.http://www.ncbi.nlm.nih.gov/pubmed/28648512?tool=bestpractice.com[27]Dacou-Voutetakis C, Feltquate DM, Drakopoulou M, et al. Familial hypothyroidism caused by a nonsense mutation in the thyroid-stimulating hormone beta-subunit gene. Am J Hum Genet. 1990;46:988.http://www.ncbi.nlm.nih.gov/pubmed/1971148?tool=bestpractice.com