The R450H Mutation and D727E Polymorphism of the Thyrotropin Receptor Gene in a Chinese Child with Congenital Hypothyroidism
The R450H Mutation and D727E Polymorphism of the Thyrotropin Receptor Gene in a Chinese Child with Congenital Hypothyroidism
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DOI：
10.1515/jpem.2010.209
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发表时间：
2010-12-01
影响因子：
1.4
通讯作者：
Yu, Wei-nan
中科院分区：
文献类型：
--
作者：
Ma, Shao-gang;Fang, Pei-hua;Yu, Wei-nan
背景：先天性甲状腺功能减退症（CH）是最常见的先天性内分泌疾病。大多数新生儿CH的分子原因尚不清楚。为探讨先天性甲状腺功能减退症（CH）患儿促甲状腺激素受体（TSHR）基因突变及其遗传特点，对18例CH患儿和105例正常对照进行TSHR基因的分子检测。采用单链构象多态性（PCR-SSCP）方法检测TSHR基因第1-9、10外显子，并进行测序。1例12岁腺体发育不良患儿的SSCP表现为先慢后快的移动性改变。TSHR基因测序结果显示存在一个纯合突变（CGC -> CAC，Arg 450 His）和一个多态性（GAC -> GAG，Asp 727 Glu）。对照组未发现变异。对先证者的12名亲属进行调查。其父母等6名亲属TSHR基因R450 H突变和D 727 E多态性均为杂合子。甲状腺激素水平正常，但循环TSH（5。96-6.杂合子家系中6名成员血清中G1、G2、G3、G4、G5、G6、G9、G10、G1 TSHR基因纯合突变R450 H导致CH，杂合突变R450 H导致亚临床甲减。
Background: Congenital hypothyroidism (CH) is the most prevalent congenital endocrine disorder. The molecular cause of CH in the majority of newborns is unknown. The aim of this study was to investigate the mutation of thyrotropin receptor (TSHR) gene in Chinese children with congenital hypothyroidism (CH) and the hereditary characteristic.Methods: Eighteen Chinese children with CH were enrolled for molecular analysis of the TSHR gene and 105 normal controls were evaluated. The exons 1-9, and 10 of TSHR gene were detected by PCR-SSCP (single-stranded conformation polymorphism) and sequenced.Results. A slower and a faster mobility SSCP shift showed in a 12-year old child with hypoplasic gland. Sequencing of TSHR gene revealed a homozygous mutation (CGC -> CAC, Arg450His) and a polymorphism (GAC -> GAG, Asp727Glu). The controls revealed no variants. The 12 relatives of the proband were enrolled and investigated. Six relatives, including his mother and father, were heterozygous for R450H mutation and D727E polymorphism of the TSHR gene. Thyroid hormone levels were normal except for circulating TSH (5. 96-6. 92mU/L) level slightly elevated in six heterozygous family members.Conclusions. Homozygous mutation R450H of the TSHR gene led to CH. Heterozygous mutation R450H was the cause of subclinical hypothyroidism.