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

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 t...

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Autores principales: Yang, Fan, Wang, Dan, Zhang, Xuehua, Fan, Haoqin, Zheng, Yu, Xiao, Zhenghui, Chen, Zhi, Xiao, Yunbin, Liu, Qiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868236/
https://www.ncbi.nlm.nih.gov/pubmed/36698945
http://dx.doi.org/10.3389/fcvm.2022.1058569
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author Yang, Fan
Wang, Dan
Zhang, Xuehua
Fan, Haoqin
Zheng, Yu
Xiao, Zhenghui
Chen, Zhi
Xiao, Yunbin
Liu, Qiming
author_facet Yang, Fan
Wang, Dan
Zhang, Xuehua
Fan, Haoqin
Zheng, Yu
Xiao, Zhenghui
Chen, Zhi
Xiao, Yunbin
Liu, Qiming
author_sort Yang, Fan
collection PubMed
description 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, five mutation sites in the SARS2 gene have been identified. We used whole-exome sequencing and Sanger sequencing to find and validate a novel compound heterozygous variants of SARS2 [c.1205G>A (p.Arg402His) and c.680G>A (p.Arg227Gln)], and in silico 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.
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spelling pubmed-98682362023-01-24 Novel variants of seryl-tRNA synthetase resulting in HUPRA syndrome featured in pulmonary hypertension Yang, Fan Wang, Dan Zhang, Xuehua Fan, Haoqin Zheng, Yu Xiao, Zhenghui Chen, Zhi Xiao, Yunbin Liu, Qiming Front Cardiovasc Med Cardiovascular Medicine 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, five mutation sites in the SARS2 gene have been identified. We used whole-exome sequencing and Sanger sequencing to find and validate a novel compound heterozygous variants of SARS2 [c.1205G>A (p.Arg402His) and c.680G>A (p.Arg227Gln)], and in silico 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. Frontiers Media S.A. 2023-01-09 /pmc/articles/PMC9868236/ /pubmed/36698945 http://dx.doi.org/10.3389/fcvm.2022.1058569 Text en Copyright © 2023 Yang, Wang, Zhang, Fan, Zheng, Xiao, Chen, Xiao and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Yang, Fan
Wang, Dan
Zhang, Xuehua
Fan, Haoqin
Zheng, Yu
Xiao, Zhenghui
Chen, Zhi
Xiao, Yunbin
Liu, Qiming
Novel variants of seryl-tRNA synthetase resulting in HUPRA syndrome featured in pulmonary hypertension
title Novel variants of seryl-tRNA synthetase resulting in HUPRA syndrome featured in pulmonary hypertension
title_full Novel variants of seryl-tRNA synthetase resulting in HUPRA syndrome featured in pulmonary hypertension
title_fullStr Novel variants of seryl-tRNA synthetase resulting in HUPRA syndrome featured in pulmonary hypertension
title_full_unstemmed Novel variants of seryl-tRNA synthetase resulting in HUPRA syndrome featured in pulmonary hypertension
title_short Novel variants of seryl-tRNA synthetase resulting in HUPRA syndrome featured in pulmonary hypertension
title_sort novel variants of seryl-trna synthetase resulting in hupra syndrome featured in pulmonary hypertension
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868236/
https://www.ncbi.nlm.nih.gov/pubmed/36698945
http://dx.doi.org/10.3389/fcvm.2022.1058569
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