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Inherited Selenocysteine Transfer RNA Mutation: Clinical and Hormonal Evaluation of 2 Patients
European Thyroid Journal ( IF 3.5 ) Pub Date : 2021-08-26 , DOI: 10.1159/000518275
Aurore Geslot 1 , Frédérique Savagner 2 , Philippe Caron 1
Affiliation  

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:

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
更新日期:2021-08-26
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