Expanding clinical spectrum of non-autoimmune hyperthyroidism due to an activating germline mutation, p.M453T, in the thyrotropin receptor gene
Expanding clinical spectrum of non-autoimmune hyperthyroidism due to an activating germline mutation, p.M453T, in the thyrotropin receptor gene
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DOI：
10.1111/j.1365-2265.2008.03367.x
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发表时间：
2009-04-01
影响因子：
3.2
通讯作者：
Shotelersuk, Vorasuk
中科院分区：
文献类型：
--
作者：
Supornsilchai, Vichit;Sahakitrungruang, Taninee;Shotelersuk, Vorasuk
描述一个泰国家族的非自身免疫性甲状腺功能亢进症（NAH）的临床和遗传特征，该家族由促甲状腺激素受体（TSHR）基因的激活性生殖系突变引起。从患儿外周血白细胞中提取基因组DNA，采用直接测序法对患儿及其父母TSHR基因全编码序列进行突变分析，发现TSHR基因第10外显子存在杂合子生殖系T → C突变。（c.1358T -> C）导致密码子453（p.M453T）处甲硫氨酸（ATG）被苏氨酸（ACG）取代。他们表现出不同的临床严重程度和不同的发病年龄。除了甲状腺功能亢进症，脑室扩大和第五掌骨和第五手指的中指骨的双侧缩短一致地发现在所有受影响的individuals. Aceticulomegaly和第五掌骨和第五手指的中指骨的双侧缩短可能是NAH的特征性特征，因为激活TSHR种系突变。此外，第五指中节指骨的缩短以前从未被描述过，扩大了该疾病的表型谱。
To describe clinical and genetic features of a Thai family with non-autoimmune hyperthyroidism (NAH) caused by an activating germline mutation in the thyrotropin receptor (TSHR) gene.Three affected individuals from the same family (a father and his two children) were studied. Clinical and imaging findings were reviewed and compared.Genomic DNA was extracted from peripheral blood leukocytes and mutation analysis of the entire coding sequence of the TSHR gene was performed in both children and their parents by direct DNA sequencing.A heterozygous germline T to C transition in exon 10 of the TSHR gene (c.1358T -> C) resulting in the substitution of methionine (ATG) by threonine (ACG) at codon 453 (p.M453T) was identified in the father and his two children. They presented with different clinical severity and variable age of onset. In addition to hyperthyroidism, ventriculomegaly and bilateral shortening of the fifth metacarpal bones and the middle phalanges of the fifth fingers were consistently found in all affected individuals.Ventriculomegaly and bilateral shortening of the fifth metacarpal bones and the middle phalanges of the fifth fingers might be characteristic features of NAH because of an activating TSHR germline mutation. In addition, the shortening of the middle phalanges of the fifth fingers has never been previously described, expanding the phenotypic spectrum of the disease.