A case of chronic kidney disease with pulmonary hypertension, hyperuricemia, immunodeficiency and other extrarenal findings: Answers

Göknar, Nilüfer; Keleşoğlu, Emre; Kasap, Nurhan; Uckardes, Diana; Candan, Cengiz

doi:10.1007/s00467-022-05560-y

Cited by 2 publications

(5 citation statements)

References 9 publications

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“…SARS2 gene mutations result in SerRS loss of function that leads to an inhibition of the biosynthesis of mitochondrial proteins, then results in an impaired oxidative phosphorylation (OXPHOS) system. To date, including this case, there are 5 kinds of variants of SARS2 ( 2 , 5 – 7 ). Based on former reports, homozygous variants tend to exhibit all symptoms of HUPRA syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there are no targeted therapies for HUPRA syndrome and most mitochondrial diseases ( 5 , 22 ), and most of these patients die of multiorgan failure in the early stage. The main therapies are supportive and symptomatic.…”

Section: Discussionmentioning

confidence: 99%

“…To date, eight HUPRA syndrome patients and five kinds of variants of SARS2 have been reported. Variants and clinical manifestations are summarized in Table 3 ( 2 , 5 – 7 ). All patients exhibit progressive renal failure except this case, and this case is the only compound heterozygous variants patient that prominently presents pulmonary hypertension phenotype.…”

Section: Literature Reviewmentioning

confidence: 99%

“…Thus, it’s vital to analyze pedigree and the structure of SerRS variants to identify possible mechanism or therapies. To date, five variants of SARS2 have been identified, however structure analysis of mutate enzyme has not been performed yet ( 2 , 5 – 7 ). We diagnosed a HUPRA syndrome patient that carried novel compound heterozygous variants; however, in this case, pulmonary hypertension was the main clinical feature instead of renal failure.…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Wang

Zhang

et al. 2023

Front. Cardiovasc. Med.

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Literature Reviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Yang

Wang

Zhang

et al. 2023

Front. Cardiovasc. Med.

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“…Current therapeutic approaches for mt-ARS-associated diseases include treatments for general mitochondrial disease and/or the management of specific phenotypes; for example, in a case of SARS2 -related HUPRA syndrome, the patient was treated with sildenafil for pulmonary hypertension, allopurinol for hyperuricemia, and α-lipoic acid and coenzyme Q10 for mitochondrial oxidative phosphorylation deficiencies [ 114 ]. While these drugs are treating the symptoms of HUPRA syndrome, they are not directly addressing the pathogenic mt-ARS variants.…”

Section: How Do We Develop Therapeutics For Patients With Mt-ars-rela...mentioning

confidence: 99%

The Role of Nuclear-Encoded Mitochondrial tRNA Charging Enzymes in Human Inherited Disease

Greco

Antonellis

2022

Genes

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Aminoacyl-tRNA synthetases (ARSs) are highly conserved essential enzymes that charge tRNA with cognate amino acids—the first step of protein synthesis. Of the 37 nuclear-encoded human ARS genes, 17 encode enzymes are exclusively targeted to the mitochondria (mt-ARSs). Mutations in nuclear mt-ARS genes are associated with rare, recessive human diseases with a broad range of clinical phenotypes. While the hypothesized disease mechanism is a loss-of-function effect, there is significant clinical heterogeneity among patients that have mutations in different mt-ARS genes and also among patients that have mutations in the same mt-ARS gene. This observation suggests that additional factors are involved in disease etiology. In this review, we present our current understanding of diseases caused by mutations in the genes encoding mt-ARSs and propose explanations for the observed clinical heterogeneity.

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A case of chronic kidney disease with pulmonary hypertension, hyperuricemia, immunodeficiency and other extrarenal findings: Answers

Cited by 2 publications

References 9 publications

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

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

The Role of Nuclear-Encoded Mitochondrial tRNA Charging Enzymes in Human Inherited Disease

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