Hypothyroidism in a Brazilian kindred due to iodide trapping defect caused by a homozygous mutation in the sodium/iodide symporter gene
Hypothyroidism in a Brazilian kindred due to iodide trapping defect caused by a homozygous mutation in the sodium/iodide symporter gene
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DOI：
10.1006/bbrc.1997.7594
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发表时间：
1997-11-17
影响因子：
3.1
通讯作者：
Refetoff, S
中科院分区：
文献类型：
--
作者：
Pohlenz, J;MedeirosNeto, G;Refetoff, S
一名患有大甲状腺肿的 36 岁男性因甲状腺和唾液腺放射性碘摄取量低而被怀疑患有碘化物 (I-) 转运缺陷。由于甲状腺细胞学检查无法排除恶性肿瘤，因此进行了甲状腺手术。对源自甲状腺 mRNA 的整个 Na+/I- 同向转运蛋白 (NIS) cDNA 进行测序，结果显示核苷酸 (nt) 1163 中的正常胞嘧啶被腺嘌呤纯合取代，导致密码子 272 处终止 (TGA)。这种无义突变产生截短的 NIS，当表达到 COS-7 细胞中时，其 I- 转运活性无法检测。基因分型证实，这名男子的突变是纯合的，而他未受影响的母亲、儿子和姑妈是杂合的。在 50 个正常个体中均未检测到这种 nt 取代，从而排除了多态性。虽然纯合突变体 NIS-272X 会导致先天性甲状腺功能减退症，但异合子 (C272X) 中一种正常等位基因的表达足以维持活跃的甲状腺 I- 摄取和功能。 (C) 1997 年学术出版社。
A 36 year old man with a large goiter was suspected of having iodide (I-) transport defect based on low thyroidal and salivary gland radioiodide uptake. Thyroid surgery was performed, because thyroid cytology could not exclude a malignancy. Sequencing of the entire Na+/I- symporter (NIS) cDNA derived from thyroidal mRNA revealed a homozygous substitution of the normal cytosine in nucleotide (nt) 1163 with an adenine, resulting in a stop (TGA) at codon 272. This nonsense mutation produces a truncated NIS with undetectable I- transport activity when expressed into COS-7 cells. Genotyping confirmed that the propositus was homozygous for the mutation whereas his unaffected mother, son, and paternal aunt were heterozygous. This nt substitution was not detected in any of 50 normal individuals, ruling out a polymorphism. While the homozygous mutant NIS-272X causes congenital hypothyroidism, expression of one normal allele in the heterogygote (C272X) is sufficient to maintain active thyroidal I- uptake and function. (C) 1997 Academic Press.