Background and purpose

Mitochondrial aminoacyl-tRNA synthetases—encoded by ARS2 genes—are evolutionarily conserved enzymes that catalyse the attachment of amino acids to their cognate tRNAs, ensuring the accuracy of the mitochondrial translation process. ARS2 gene mutations are associated with a wide range of clinical presentations affecting the CNS.

Methods

Two senior neuroradiologists analysed brain MRI of 25 patients (age range: 3 d–25 yrs.; 11 males; 14 females) with biallelic pathogenic variants of 11 ARS2 genes in a retrospective study conducted between 2002 and 2019.

Results

Though several combinations of brain MRI anomalies were highly suggestive of specific aetiologies (DARS2, EARS2, AARS2 and RARS2 mutations), our study detected no MRI pattern common to all patients. Stroke-like lesions were associated with pathogenic SARS2 and FARS2 variants. We also report early onset cerebellar atrophy and calcifications in AARS2 mutations, early white matter involvement in RARS2 mutations, and absent involvement of thalami in EARS2 mutations. Finally, our findings show that normal brain MRI results do not exclude the presence of ARS2 mutations: 5 patients with normal MRI images were carriers of pathogenic IARS2, YARS2, and FARS2 variants.

Conclusion

Our study extends the spectrum of brain MRI anomalies associated with pathogenic ARS2 variants and suggests ARS2 mutations are largely underdiagnosed.

中文翻译：

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线粒体氨酰-tRNA合成酶突变中脑MRI模式的表型多样性

背景和目的

由 ARS2 基因编码的线粒体氨酰 tRNA 合成酶是进化上保守的酶，可催化氨基酸与其同源 tRNA 的连接，确保线粒体翻译过程的准确性。ARS2 基因突变与影响 CNS 的多种临床表现有关。

方法

在 2002 年至 2019 年期间进行的一项回顾性研究中，两名资深神经放射科医生分析了 25 名患者（年龄范围：3 天至 25 岁；11 名男性；14 名女性）的脑部 MRI，这些患者具有 11 个 ARS2 基因的双等位基因致病变异。

结果

尽管脑部 MRI 异常的几种组合高度提示特定病因（DARS2、EARS2、AARS2和RARS2突变），但我们的研究未检测到所有患者共有的 MRI 模式。中风样病变与致病性SARS2和FARS2变异相关。我们还报告了AARS2突变中早发性小脑萎缩和钙化、RARS2突变中早期白质受累以及EARS2 中没有丘脑受累突变。最后，我们的研究结果表明，正常的脑部 MRI 结果并不能排除 ARS2 突变的存在：5 名具有正常 MRI 图像的患者是致病性IARS2、YARS2和FARS2变异的携带者。

结论

我们的研究扩展了与致病性 ARS2 变异相关的脑 MRI 异常的范围，并表明 ARS2 突变在很大程度上未被诊断出来。