Yang Fan, Wang Dan, Zhang Xuehua, Fan Haoqin, Zheng Yu, Xiao Zhenghui, Chen Zhi, Xiao Yunbin, Liu Qiming
Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, China.
Department of Cardiology, Hunan Children's Hospital, Changsha, China.
Front Cardiovasc Med. 2023 Jan 9;9:1058569. doi: 10.3389/fcvm.2022.1058569. eCollection 2022.
Hyperuricemia, pulmonary hypertension, and renal failure in infancy and alkalosis syndrome (HUPRA syndrome) is an ultrarare mitochondrial disease that is characterized by hyperuricemia, pulmonary hypertension, renal failure, and alkalosis. Seryl-tRNA synthetase 2 () gene variants are believed to cause HUPRA syndrome, and these variants result in the loss of function of seryl-tRNA synthetase. Eventually, mutated seryl-tRNA synthetase is unable to catalyze tRNA synthesis and leads to the inhibition of the biosynthesis of mitochondrial proteins. This causes oxidative phosphorylation (OXPHOS) system impairments. To date, five mutation sites in the gene have been identified. We used whole-exome sequencing and Sanger sequencing to find and validate a novel compound heterozygous variants of [c.1205G>A (p.Arg402His) and c.680G>A (p.Arg227Gln)], and analysis to analyze the structural change of the variants. We found that both variants were not sufficient to cause obvious structural damage but changed the intermolecular bond of the protein, which could be the cause of HUPRA syndrome in this case. We also performed the literature review and found this patient had significant pulmonary hypertension and minor renal dysfunction compared with other reported cases. This study inspired us to recognize HUPRA syndrome and broaden our knowledge of gene variation in PH.
婴儿期高尿酸血症、肺动脉高压和肾衰竭及碱中毒综合征（HUPRA综合征）是一种极为罕见的线粒体疾病，其特征为高尿酸血症、肺动脉高压、肾衰竭和碱中毒。丝氨酰 - tRNA合成酶2（）基因变异被认为会导致HUPRA综合征，这些变异会导致丝氨酰 - tRNA合成酶功能丧失。最终，突变的丝氨酰 - tRNA合成酶无法催化tRNA合成，导致线粒体蛋白质生物合成受到抑制。这会引起氧化磷酸化（OXPHOS）系统损伤。迄今为止，已在该基因中鉴定出五个突变位点。我们使用全外显子组测序和桑格测序来发现并验证一种新的[ c.1205G>A（p.Arg402His）和c.680G>A（p.Arg227Gln）]复合杂合变异，并通过分析来分析这些变异的结构变化。我们发现这两种变异都不足以导致明显的结构损伤，但改变了蛋白质的分子间键，这可能是该病例中HUPRA综合征的病因。我们还进行了文献综述，发现与其他报告病例相比，该患者有显著的肺动脉高压和轻微的肾功能障碍。这项研究促使我们认识HUPRA综合征，并拓宽了我们对肺动脉高压基因变异的认识。
