Clinical significance of heterozygous carriers associated with compensated hypothyroidism in R450H, a common inactivating mutation of the thyrotropin receptor gene in Japanese

被引:15
作者
Kanda, Keisuke
Mizuno, Haruo
Sugiyama, Yukari
Imamine, Hiroki
Togari, Hajime
Onigata, Kazumichi
机构
[1] Nagoya City Univ, Grad Sch Med Sci, Dept Pediat Neonatol & Congenital Disorders, Mizuho Ku, Nagoya, Aichi 4678601, Japan
[2] Gunma Univ, Grad Sch Med, Dept Pediat & Dev Med, Gunma, Japan
关键词
thyrotropin receptor gene; TSH resistance; heterozygous; congenital hypothyroidism; inactivating mutation;
D O I
10.1007/s12020-006-0018-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Loss-of-function mutations in the thyrotropin receptor (TSHR) gene were described as a syndrome characterized by thyroid hyposensivity to biologically active TSH, ranging from euthyroid to severe hypothyroidism. In Japanese, a common mutation in the TSHR gene is R450H, which demonstrated moderately impaired receptor function. We studied six subjects of Japanese origin whose major abnormality was persistent hyperthyrotropinemia by genetic sequence analysis of the TSH R gene. Three subjects were homozygous for the R450H mutation, whereas the three remaining subjects were single heterozygous. Homozygous subjects displayed mild hypothyroidism confirmed by moderately elevated basal TSH levels and excessive TSH response to TRH administration. Heterozygous subjects also demonstrated fully or partially compensated hypothyroidism, but less severe than that of homozygous subjects. More frequent involvement of the R450H mutation in the TSHR gene in Japanese was identified. in addition, a good correlation between phenotype and genotype was demonstrated in respect to biochemical analysis and drug dosage. Our observations showed clinical significance of heterozygosity associated with compensated hypothyroidism in spite of only mildly impaired receptor function.
引用
收藏
页码:383 / 388
页数:6
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