Pardo Viviane, Rubio Ileana G S, Knobel Meyer, Aguiar-Oliveira Manoel H, Santos Marcos M, Gomes Simone A, Oliveira Carla R P, Targovnik Hector M, Medeiros-Neto Geraldo
Thyroid Study Unit (LIM-25), Division of Endocrinology, University of São Paulo Medical School, São Paulo, Brazil.
Thyroid. 2008 Jul;18(7):783-6. doi: 10.1089/thy.2007.0321.
Thyroglobulin (Tg) is a large glycoprotein that is intimately involved in the biosynthesis of thyroxine and triiodothyronine. At least 38 mutations have been described in the Tg gene that are associated with varying degrees of hypothyroidism. We studied the Tg gene in four related subjects with congenital hypothyroidism.
We found a novel compound heterozygous constellation (IVS30 + 1G>T/A2215D) in a brother and sister and one previously described related mutation (IVS30+1G>T) in their two sibling second degree cousins. The brother with the IVS30 + 1G>T/A2215D mutation and the two siblings with the IVS30+1G>T mutation had fetal or neonatal goiter and all had hypothyroidism.
This study further confirms the association of the IVS30+G>T mutation of the Tg gene with hypothyroidism. Computer analysis predicts that the A2215D mutation, first reported here, should cause structural instability of Tg but when present as a compound heterozygous mutation with IVS30+G>T/A its effect is unclear but is likely to be influenced by iodine intake.
甲状腺球蛋白（Tg）是一种大型糖蛋白，密切参与甲状腺素和三碘甲状腺原氨酸的生物合成。已在Tg基因中描述了至少38种突变，这些突变与不同程度的甲状腺功能减退有关。我们对四名患有先天性甲状腺功能减退的相关受试者的Tg基因进行了研究。
我们在一名兄妹中发现了一种新的复合杂合子组合（IVS30 + 1G>T/A2215D），在他们的两个二级堂兄弟姐妹中发现了一个先前描述的相关突变（IVS30+1G>T）。携带IVS30 + 1G>T/A2215D突变的哥哥以及携带IVS30+1G>T突变的两个兄弟姐妹患有胎儿或新生儿甲状腺肿，且均患有甲状腺功能减退。
本研究进一步证实了Tg基因的IVS30+G>T突变与甲状腺功能减退之间的关联。计算机分析预测，此处首次报道的A2215D突变应会导致Tg的结构不稳定，但当与IVS30+G>T/A作为复合杂合突变出现时，其影响尚不清楚，但可能受碘摄入量的影响。
