AUTHOR=Yang Fan , Wang Dan , Zhang Xuehua , Fan Haoqin , Zheng Yu , Xiao Zhenghui , Chen Zhi , Xiao Yunbin , Liu Qiming 

TITLE=Novel variants of seryl-tRNA synthetase resulting in HUPRA syndrome featured in pulmonary hypertension

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1058569

DOI=10.3389/fcvm.2022.1058569

ISSN=2297-055X

ABSTRACT=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 (SARS2) 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, 5 mutation sites in the SARS2 gene have been identified. In this study, we discover a novel SARS2 variant that is related to HUPRA syndrome. Whole-exome sequencing revealed novel compound heterozygous variants of SARS2 (c.1205G>A (p.Arg402His) and c.680G>A (p.Arg227Gln)). Computational prediction confirmed that c.680G>A was a novel variant and graded as variants of uncertain significance (VUS). Moreover, this patient had significant pulmonary hypertension and minor renal dysfunction compared with other reported cases.