Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions.
Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions.
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对变体甲状腺素结合球蛋白（TBG）-圣地亚哥的测序揭示了两个核苷酸取代。
DOI：
10.1016/0925-4439(92)90105-v
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Refetoff,S
中科院分区：
文献类型：
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作者：
Bertenshaw,R;Sarne,D;Tornari,J;Weinberg,M;Refetoff,S
甲状腺素结合球蛋白（TBG）是一种肝脏糖蛋白，转运血清中的甲状腺激素。1989年，报道了一种变异TBG，其与甲状腺素（T4）和三碘甲状腺胺（T3）的结合亲和力降低，导致血清T4和T3水平降低。这种变体TBG-San Diego（TBG-SD）也显示出降低的热稳定性，但具有正常的等电聚焦模式。我们现在报告TBG-San Diego的整个编码区的序列。它揭示了两个核苷酸取代：一个位于外显子1，导致正常的Ser-23（TCA）被苏氨酸（ACA）取代，另一个位于外显子3，TTG（亮氨酸）的正常密码子283被TTT（苯丙氨酸）取代。等位基因特异性扩增被用来寻找这两个核苷酸取代在四个受影响的家庭成员。结果证实了这些核苷酸取代与TBG-SD表型的共分离。密码子283中的取代先前已被描述，并且在一些种族群体中作为多态性存在或与具有不同物理特征的其他TBG变体组合存在。因此，看来丝氨酸-23与苏氨酸的替代是TBG-San Diego的物理性质的观察到的改变的原因。
Thyroxine-binding globulin (TBG) is a liver glycoprotein that tranports thyroid hormone in serum. In 1989, a variant TBG was reported with reduced binding affinity for thyroxine (T 4) and triidothyromine (T 3) which results in low serum T 4 and T 3 levels. This variant, TBG-San Diego (TBG-SD), also displays reduced heat stability but has a normal isoelectric focusing pattern. We now report the sequence of the entire coding region of TBG-San Diego. It reveals two nucleotide substitutions: one located in exon 1 which results in the replacement of the normal Ser-23 (TCA) with threonin (A CA) and the other, located in exon 3, changes the normal codon 283 of TTG (Leucine) with that of TTT,(phenylalanine). Allele specific amplication was used to search for both nucleotide substitutions in four affected members of the family. Results confirmed the co-segregation of these nucleotide substitutions with the TBG-SD phenotype. The substitution in codon 283 has been previously described and exists as a polymorphism in some ethnic groups or in combination with other TBG variants with different physical characteristics. Thus, it appears that the replacement of Ser-23 with threonine is responsible for the observed alterations in physical properties of TBG-San Diego.