PDF(Pubmed)
Abstract：
Aminoacyl-tRNA synthetases play a pivotal role in catalyzing the precise coupling of amino acids with their corresponding tRNAs. Among them, Tyrosyl tRNA synthetase, encoded by the YARS1 gene, facilitates the aminoacylation of tyrosine to its designated tRNA. Heterozygous variants in the YARS1 gene have been linked to autosomal dominant Charcot-Marie-Tooth type C, while recent findings have unveiled biallelic YARS1 variants leading to an autosomal recessive multisystemic disorder in several cases. In this report, we present a novel case characterized by dysmorphic facies, and multisystemic symptoms, prominently encompassing neurological issues and a microarray conducted shortly after birth revealed 47, XXY. Utilizing whole exome sequencing, we uncovered a paternally inherited likely pathogenic variant (c.1099C > T, p.Arg367Trp), previously reported, coinciding with the father\'s history of hearing loss and neurological symptoms. Additionally, a maternally inherited variant of uncertain significance (c.782T > G, p.Leu261Arg), previously unreported, was identified within the YARS1 gene. The observed phenotypes and the presence of compound heterozygous results align with the diagnosis of an autosomal recessive disorder associated with YARS1. Through our cases, the boundaries of this emerging clinical entity are broadened. This instance underscores the significance of comprehensive genetic testing in patients exhibiting intricate phenotypes.
摘要：
氨酰-tRNA合成酶在催化氨基酸与其相应的tRNA的精确偶联中起关键作用。其中,酪氨酸tRNA合成酶,由YARS1基因编码，促进酪氨酸氨基酰化为其指定的tRNA。YARS1基因中的杂合变体已与常染色体显性遗传Charcot-Marie-ToothC型相关，虽然最近的研究结果揭示了双等位基因YARS1变异在几个病例中导致常染色体隐性多系统疾病。在这份报告中,我们提出了一个以异形相为特征的新颖案例，和多系统症状，突出包括神经系统问题，出生后不久进行的微阵列显示47，XXY。利用整个外显子组测序，我们发现了一种父系遗传的可能致病变异(c.1099C>T，p.Arg367Trp),此前报道,与父亲的听力损失史和神经症状相吻合。此外,一种意义不确定的母系遗传变体(c.782T>G，p.Leu261Arg)，以前没有报道，在YARS1基因中鉴定。观察到的表型和复合杂合结果的存在与YARS1相关的常染色体隐性遗传疾病的诊断一致。通过我们的案例,这一新兴临床实体的界限扩大了.这个例子强调了在表现出复杂表型的患者中进行全面基因检测的重要性。
