Introduction: Iodothyronine deiodinases are selenoproteins with the amino acid selenocysteine (Sec) introduced into the position of a TGA stop codon by a complex machinery involving tRNA^[Ser]Sec when a cis-acting Sec-insertion sequence element is present in the 3′ end of the mRNA. Recently, a variant in the TRU-TCA1-1 gene encoding for tRNA^[Ser]Sec was reported, which resulted in reduced expression of stress-related selenoproteins. The proband presented with multisystem symptoms, euthyroid hyperthyroxinemia, and selenium deficiency. Here, we describe 2 new members of a family harboring the same tRNA^[Ser]Sec variant. Case Presentation: A 13-year-old patient was seen for Hashimoto’s disease with high FT3 (4.6 pg/mL, normal range 2–4.2 pg/mL) and normal FT4 and TSH concentrations. He had no clinical complaints. During a 6-year clinical and hormonal follow-up, the index patient was not treated, FT3 decreased, FT4 increased, and serum TSH stayed in the normal range resulting in a euthyroid hyperthyroxinemia. Reverse T3 concentration was significantly increased at the last visit (19 years and 4 months). At the last evaluation, the total selenium level was low (91 μg/L, normal range 95–125). DNA sequencing identified a germinal homozygous variant (C65G) in the TRU-TCA1-1 gene. During follow-up, no additional clinical symptom was observed in the absence of any treatment. The same germinal tRNA^[Ser]Sec variant was identified at heterozygous state in his father, who had normal thyroid function tests except a moderately increased reverse T3 concentration, with increased total selenium (143 μg/L) level. In both patients, the expression of stress-related selenoprotein GPX3 was in the low-normal range (168 and 180 IU/L, respectively, normal range: 150–558 IU/L). We did not find any significant biological abnormalities evocative of other selenoprotein deficiencies. Discussion/Conclusion: We report on 2 members of a family with a variant in the TRU-TCA1-1 gene encoding for tRNA^[Ser]Sec. Our study suggests that this tRNA^[Ser]Sec variant is not exclusively causative of disruption in selenoprotein synthesis.
Eur Thyroid J

中文翻译：

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遗传性硒代半胱氨酸转移 RNA 突变：2 名患者的临床和激素评估

简介：碘甲状腺原氨酸脱碘酶是一种硒蛋白，当 3' 端存在顺式作用的 Sec 插入序列元件时，^{通过涉及 tRNA [Ser]Sec}的复杂机制将氨基酸硒代半胱氨酸 (Sec) 引入 TGA 终止密码子的位置的mRNA。最近，^{报道了编码 tRNA [Ser]Sec的}TRU-TCA1-1基因，这导致与压力相关的硒蛋白的表达减少。先证者出现多系统症状，甲状腺功能正常的高甲状腺素血症和硒缺乏。在这里，我们描述了一个拥有相同 tRNA ^[Ser]Sec变体的家族的 2 个新成员。案例介绍：一名 13 岁的桥本氏病患者出现高 FT3（4.6 pg/mL，正常范围 2-4.2 pg/mL）和正常 FT4 和 TSH 浓度。他没有临床症状。在 6 年的临床和激素随访期间，指示患者未接受治疗，FT3 降低，FT4 升高，血清 TSH 保持在正常范围内，导致甲状腺功能正常的高甲状腺素血症。最后一次访视（19 年零 4 个月）时，反向 T3 浓度显着增加。在最后一次评估中，总硒水平较低（91 μg/L，正常范围 95-125）。DNA 测序鉴定了TRU-TCA1-1基因中的生发纯合变体 (C65G)。在随访期间，在没有任何治疗的情况下没有观察到额外的临床症状。相同的生发 tRNA ^[Ser]Sec在他父亲的杂合状态下发现了变异，他的父亲甲状腺功能测试正常，但反向 T3 浓度适度增加，总硒（143 μg/L）水平增加。在这两名患者中，应激相关硒蛋白 GPX3 的表达均处于低正常范围（分别为 168 和 180 IU/L，正常范围：150-558 IU/L）。我们没有发现任何引起其他硒蛋白缺乏的显着生物学异常。讨论/结论：我们报告了一个家族的 2 个成员，其TRU-TCA1-1基因编码 tRNA ^[Ser]Sec的变异。我们的研究表明，这种 tRNA ^[Ser]Sec变体并不是硒蛋白合成中断的唯一原因。
欧洲甲状腺杂志