Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene
Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene
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DOI：
10.1515/jpem-2014-0078
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发表时间：
2015-05-01
影响因子：
1.4
通讯作者：
Saji, Tsutomu
中科院分区：
文献类型：
--
作者：
Satoh, Mari;Aso, Keiko;Saji, Tsutomu
促甲状腺激素受体（TSHR）基因突变杂合子的受试者表现出从甲状腺功能正常到高促甲状腺素血症的各种表型。同样，杂合双氧化酶2（DUOX 2）基因突变导致不同的表型，如短暂性先天性甲状腺功能减退症，亚临床高促甲状腺素血症和儿童甲状腺功能正常。在这里，我们描述了一个8岁的男孩谁有正常的新生儿筛查结果，但谁开发的非自身免疫性甲状腺功能减退症在1岁8个月的年龄。他是杂合子为先前报告的R450 H-TSHR突变和杂合子为一个新的双突变等位基因A1323 T-DUOX 2和L1343 F-DUOX 2。他需要左旋甲状腺素（l-T4）替代疗法以将血清TSH水平保持在正常范围内; 2.01-2.65 μ g/kg/天的l-T4剂量对应于R450 H-TSHR纯合子儿童和患有永久性先天性甲状腺功能减退症的儿童所服用的剂量。因此，杂合TSHR突变和杂合DUOX 2突变的共存可能影响了他甲状腺功能减退症的严重程度。
Subjects who are heterozygous for thyroid stimulating hormone receptor (TSHR) gene mutations present various phenotypes that range from euthyroid to hyperthyrotropinemia. Similarly, heterozygous dual oxidase 2 (DUOX2) gene mutations result in variable phenotypes, such as transient congenital hypothyroidism, subclinical hyperthyrotropinemia, and euthyroid in children. Here, we describe an 8-year-old boy who had normal newborn screening results, but who developed nonautoimmune hypothyroidism at the age of 1 year and 8 months of age. He was heterozygous for previously reported R450H-TSHR mutation and heterozygous for a novel double mutant allele A1323T-DUOX2 and L1343F-DUOX2. He needed levothyroxine (l-T4) replacement therapy to keep serum TSH levels within normal limits; l-T4 dose of 2.01-2.65 mu g/kg/day corresponded to the dose taken by children homozygous for R450H-TSHR and by children with permanent congenital hypothyroidism. Therefore, the coexistence of a heterozygous TSHR mutation and a heterozygous DUOX2 mutation may have affected the severity of his hypothyroid condition.