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A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: a case report and review of the literature

  • Bo-Yun Yang
  • Han-Xiao Yu
  • Jie Min
  • Xiao-Xiao SongEmail author
Case Based Review
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Abstract

Pyrophosphate synthetase-1(PRS-1) is a crucial enzyme that catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) with substrate: adenosine triphosphate (ATP) and ribose-5-phophate(R5P) in the de novo pathways of purine and pyrimidine nucleotide synthesis. Mutation in PRPS1 can result in a series of diseases of purine metabolism, which includes PRS-1 superactivity. The common clinical phenotypes are hyperuricemia and hyperuricosuria. We identified a novel missense mutation in X-chromosomal gene PRPS1 in a young Chinese woman while her mother has heterogeneous genotype and phenotype. A 24-year-old Chinese female patient suffered hyperuricemia, gout, and recurrent hyperpyrexia for more than 6 years, and then was diagnosed with hyperandrogenism, insulin resistance (IR), and polycystic ovary syndrome (PCOS). A novel missense mutation, c.521(exon)G>T, p.(Gly174Val) was detected by next-generation sequencing (NGS) and confirmed by Sanger sequencing in the patient and her parents. Interestingly, her mother has the same heterozygous missense mutation but without uric acid overproduction which can be explained by the phenomenon of the skewed X-chromosome inactivation. The substituted amino acid Val for Gly174 is positioned in the pyrophosphate (PPi) binding loop, and this mutation impacts the binding rate of Mg2+-ATP complex to PRS-1, thus the assembling of homodimer is affected by changed Val174 leading to the instability of the allosteric site. Our report highlights the X-linked inheritance of gout in females caused by mutation in PRPS1 accompanied with severe metabolic disorders and recurrent hyperpyrexia.

Keywords

Gout Metabolism disorder PRPS1 PRS-1 superactivity 
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Notes

Acknowledgments

We thank the proband and her family for collaboration in this study. We thank the Chigene (Beijing) Translational Medical Research Center Co. Ltd for great help in genetic testing.

Funding

This work was supported by a grant from Science Technology Department of Zhejiang Province of China (grant number 2012R10038 to Xiao-Xiao Song), a grant from Zhejiang Provincial Medical and Health Technology Project (grant number 2013KYA089 to Xiao-Xiao Song), and a grant from National Natural Science Foundation of China (grant number 81300083 to Xiao-Xiao Song).

Compliance with ethical standards

Disclosures

None.

Ethics statement

This study was approved by the Ethnic Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine. This study was performed according to the Helsinki Declaration. Written informed consent was obtained from the proband and her parents for the publication of this case report

Disclaimer

The funders had no role in study design, date collection and analysis, decision to publish or preparation of the manuscript.

References

  1. 1.
    Kornberg A, Lieberman I, Simms ES (1955) Enzymatic synthesis and properties of 5-phosphoribosylpyrophosphate. J Biol Chem 215(1):389–402PubMedGoogle Scholar
  2. 2.
    Holmes EW, McDonald JA, McCord JM, Wyngaarden JB, Kelley WN (1973) Human glutamine phosphoribosylpyrophosphate amidotransferase. Kinetic and regulatory properties. J Biol Chem 248(1):144–150PubMedGoogle Scholar
  3. 3.
    Tatibana M, Shigesada K (1972) Two carbamyl phosphate synthetases of mammals: specific roles in control of pyrimidine and urea biosynthesis. Adv Enzym Regul 10:249–271CrossRefGoogle Scholar
  4. 4.
    Hartman SC, Buchanan JM (1958) Biosynthesis of the purines. XXI. 5-Phosphoribosylpyrophosphate amidotransferase. J Biol Chem 233(2):451–455PubMedGoogle Scholar
  5. 5.
    Fox IH, Kelley WN (1971) Human phosphoribosylpyrophosphate synthetase. Distribution, purification, and properties. J Biol Chem 246(18):5739–5748PubMedGoogle Scholar
  6. 6.
    Liu X, Han D, Li J, Han B, Ouyang X, Cheng J, Li X, Jin Z, Wang Y, Bitner-Glindzicz M, Kong X, Xu H, Kantardzhieva A, Eavey RD, Seidman CE, Seidman JG, Du LL, Chen ZY, Dai P, Teng M, Yan D, Yuan H (2010)Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2. Am J Hum Genet 86(1):65–71.  https://doi.org/10.1016/j.ajhg.2009.11.015 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Yan D, Xing Y, Ouyang X, Zhu J, Chen ZY, Lang H, Liu XZ (2012) Analysis of miR-376 RNA cluster members in the mouse inner ear. Int J Exp Pathol 93(6):450–457.  https://doi.org/10.1111/j.1365-2613.2012.00840.x CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Chen P, Li J, Ma J, Teng M, Li X (2013) A small disturbance, but a serious disease: the possible mechanism of D52H-mutant of human PRS1 that causes gout. IUBMB Life 65(6):518–525.  https://doi.org/10.1002/iub.1154 CrossRefPubMedGoogle Scholar
  9. 9.
    Mittal R, Patel K, Mittal J, Chan B, Yan D, Grati M, Liu XZ (2015) Association of PRPS1 mutations with disease phenotypes. Dis Markers 2015:127013.  https://doi.org/10.1155/2015/127013 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Yen RC, Adams WB, Lazar C, Becker MA (1978) Evidence for X-linkage of human phosphoribosylpyrophosphate synthetase. Proc Natl Acad Sci U S A 75(1):482–485CrossRefGoogle Scholar
  11. 11.
    Becker MA, Raivio KO, Bakay B, Adams WB, Nyhan WL (1980) Variant human phosphoribosylpyrophosphate synthetase altered in regulatory and catalytic functions. J Clin Invest 65(1):109–120.  https://doi.org/10.1172/jci109640 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Becker MA, Losman MJ, Wilson J, Simmonds HA (1986) Superactivity of human phosphoribosyl pyrophosphate synthetase due to altered regulation by nucleotide inhibitors and inorganic phosphate. Biochim Biophys Acta 882(2):168–176.  https://doi.org/10.1016/0304-4165(86)90151-0 CrossRefPubMedGoogle Scholar
  13. 13.
    Becker MA (2001) Phosphoribosylpyrophosphate synthetase and the regulation of phosphoribosylpyrophosphate production in human cells. Prog Nucleic Acid Res Mol Biol 69:115–148CrossRefGoogle Scholar
  14. 14.
    Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK (2013) Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 98(12):4565–4592.  https://doi.org/10.1210/jc.2013-2350 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    (2012) Standards of medical care in diabetes--2012. Diabetes Care 35 Suppl 1:S11-S63.  https://doi.org/10.2337/dc12-s011
  16. 16.
    Li S, Lu Y, Peng B, Ding J (2007) Crystal structure of human phosphoribosylpyrophosphate synthetase 1 reveals a novel allosteric site. Biochem J 401(1):39–47.  https://doi.org/10.1042/bj20061066 CrossRefPubMedGoogle Scholar
  17. 17.
    de Brouwer AP, Williams KL, Duley JA, van Kuilenburg AB, Nabuurs SB, Egmont-Petersen M, Lugtenberg D, Zoetekouw L, Banning MJ, Roeffen M, Hamel BC, Weaving L, Ouvrier RA, Donald JA, Wevers RA, Christodoulou J, van Bokhoven H (2007) Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet 81(3):507–518.  https://doi.org/10.1086/520706 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, Weinstock GM, Wilson RK, Gibbs RA, Kent WJ, Miller W, Haussler D (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15(8):1034–1050.  https://doi.org/10.1101/gr.3715005 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Porrmann J, Betcheva-Krajcir E, Di Donato N (2017) Novel PRPS1 gain-of-function mutation in a patient with congenital hyperuricemia and facial anomalies. 173(10):2736–2742.  https://doi.org/10.1002/ajmg.a.38359 CrossRefGoogle Scholar
  20. 20.
    de Brouwer AP, van Bokhoven H, Nabuurs SB, Arts WF, Christodoulou J, Duley J (2010) PRPS1 mutations: four distinct syndromes and potential treatment. Am J Hum Genet 86(4):506–518.  https://doi.org/10.1016/j.ajhg.2010.02.024 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Karpen ME, de Haseth PL, Neet KE (1992) Differences in the amino acid distributions of 3(10)-helices and alpha-helices. Protein Sci 1(10):1333–1342.  https://doi.org/10.1002/pro.5560011013 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Garcia-Pavia P, Torres RJ, Rivero M, Ahmed M, Garcia-Puig J, Becker MA (2003) Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis Rheum 48(7):2036–2041.  https://doi.org/10.1002/art.11058 CrossRefPubMedGoogle Scholar
  23. 23.
    Roncal-Jimenez CA, Lanaspa MA, Rivard CJ, Nakagawa T, Sanchez-Lozada LG, Jalal D, Andres-Hernando A, Tanabe K, Madero M, Li N, Cicerchi C, Mc Fann K, Sautin YY, Johnson RJ (2011) Sucrose induces fatty liver and pancreatic inflammation in male breeder rats independent of excess energy intake. Metab Clin Exp 60(9):1259–1270.  https://doi.org/10.1016/j.metabol.2011.01.008 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhang Y, Yamamoto T, Hisatome I, Li Y, Cheng W, Sun N, Cai B, Huang T, Zhu Y, Li Z, Jing X, Zhou R, Cheng J (2013) Uric acid induces oxidative stress and growth inhibition by activating adenosine monophosphate-activated protein kinase and extracellular signal-regulated kinase signal pathways in pancreatic beta cells. Mol Cell Endocrinol 375(1-2):89–96.  https://doi.org/10.1016/j.mce.2013.04.027 CrossRefPubMedGoogle Scholar
  25. 25.
    Carnethon MR, Fortmann SP, Palaniappan L, Duncan BB, Schmidt MI, Chambless LE (2003) Risk factors for progression to incident hyperinsulinemia: the Atherosclerosis Risk in Communities Study, 1987-1998. Am J Epidemiol 158(11):1058–1067CrossRefGoogle Scholar
  26. 26.
    Krishnan E, Pandya BJ, Chung L, Hariri A, Dabbous O (2012) Hyperuricemia in young adults and risk of insulin resistance, prediabetes, and diabetes: a 15-year follow-up study. Am J Epidemiol 176(2):108–116.  https://doi.org/10.1093/aje/kws002 CrossRefPubMedGoogle Scholar
  27. 27.
    Gonzalez F, Rote NS, Minium J, Kirwan JP (2006) Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab 91(1):336–340.  https://doi.org/10.1210/jc.2005-1696 CrossRefPubMedGoogle Scholar
  28. 28.
    Victor VM, Rocha M, Banuls C, Alvarez A, de Pablo C, Sanchez-Serrano M, Gomez M, Hernandez-Mijares A (2011) Induction of oxidative stress and human leukocyte/endothelial cell interactions in polycystic ovary syndrome patients with insulin resistance. J Clin Endocrinol Metab 96(10):3115–3122.  https://doi.org/10.1210/jc.2011-0651 CrossRefPubMedGoogle Scholar
  29. 29.
    Fiorentino A, Fujinami K, Arno G, Robson AG, Pontikos N, Arasanz Armengol M, Plagnol V, Hayashi T, Iwata T, Parker M, Fowler T, Rendon A, Gardner JC, Henderson RH, Cheetham ME, Webster AR, Michaelides M, Hardcastle AJ (2018) Missense variants in the X-linked gene PRPS1 cause retinal degeneration in females. 39(1):80–91.  https://doi.org/10.1002/humu.23349 CrossRefGoogle Scholar
  30. 30.
    Roessler BJ, Nosal JM, Smith PR, Heidler SA, Palella TD, Switzer RL, Becker MA (1993) Human X-linked phosphoribosylpyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene. J Biol Chem 268(35):26476–26481PubMedGoogle Scholar
  31. 31.
    Almoguera B, He S, Corton M, Fernandez-San Jose P, Blanco-Kelly F, Lopez-Molina MI, Garcia-Sandoval B, Del Val J, Guo Y, Tian L, Liu X, Guan L, Torres RJ, Puig JG, Hakonarson H, Xu X, Keating B, Ayuso C (2014) Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy. Orphanet J Rare Dis 9:190.  https://doi.org/10.1186/s13023-014-0190-9 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Al-Maawali A, Dupuis L, Blaser S, Heon E, Tarnopolsky M, Al-Murshedi F, Marshall CR, Paton T, Scherer SW, Roelofsen J, van Kuilenburg AB, Mendoza-Londono R (2015) Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders. Eur J Hum Genet 23(3):310–316.  https://doi.org/10.1038/ejhg.2014.112 CrossRefPubMedGoogle Scholar
  33. 33.
    Becker MA, Smith PR, Taylor W, Mustafi R, Switzer RL (1995) The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest 96(5):2133–2141.  https://doi.org/10.1172/jci118267 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kim HJ, Sohn KM, Shy ME, Krajewski KM, Hwang M, Park JH, Jang SY, Won HH, Choi BO, Hong SH, Kim BJ, Suh YL, Ki CS, Lee SY, Kim SH, Kim JW (2007) Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5). Am J Hum Genet 81(3):552–558.  https://doi.org/10.1086/519529 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Moran R, Kuilenburg AB, Duley J, Nabuurs SB, Retno-Fitri A, Christodoulou J, Roelofsen J, Yntema HG, Friedman NR, van Bokhoven H, de Brouwer AP (2012) Phosphoribosylpyrophosphate synthetase superactivity and recurrent infections is caused by a p.Val142Leu mutation in PRS-I. Am J Med Genet A 158a(2):455–460.  https://doi.org/10.1002/ajmg.a.34428 CrossRefPubMedGoogle Scholar
  36. 36.
    Synofzik M, Muller vom Hagen J, Haack TB, Wilhelm C, Lindig T, Beck-Wodl S, Nabuurs SB, van Kuilenburg AB, de Brouwer AP, Schols L (2014)X-linkedCharcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation. Orphanet J Rare Dis 9:24.  https://doi.org/10.1186/1750-1172-9-24 CrossRefGoogle Scholar
  37. 37.
    Kim SY, Kim AR, Kim NK, Lee C, Han JH, Kim MY, Jeon EH, Park WY, Mittal R, Yan D, Liu XZ, Choi BY (2016) Functional characterization of a novel loss-of-function mutation of PRPS1 related to early-onset progressive nonsyndromic hearing loss in Koreans (DFNX1): potential implications on future therapeutic intervention. J Gene Med 18(11-12):353–358.  https://doi.org/10.1002/jgm.2935 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Becker MA, Ahmed M (2000) Cell type-specific differential expression of human PRPP synthetase (PRPS) genes. Adv Exp Med Biol 486:5–10.  https://doi.org/10.1007/0-306-46843-3_2 CrossRefPubMedGoogle Scholar
  39. 39.
    Ahmed M, Taylor W, Smith PR, Becker MA (1999) Accelerated transcription of PRPS1 in X-linked overactivity of normal human phosphoribosylpyrophosphate synthetase. J Biol Chem 274(11):7482–7488.  https://doi.org/10.1074/jbc.274.11.7482 CrossRefPubMedGoogle Scholar
  40. 40.
    Gandia M, Fernandez-Toral J, Solanellas J, Dominguez-Ruiz M, Gomez-Rosas E, Del Castillo FJ, Villamar M, Moreno-Pelayo MA, Del Castillo I (2015) Mutations in PRPS1 causing syndromic or nonsyndromic hearing impairment: intrafamilial phenotypic variation complicates genetic counseling. Pediatr Res 78(1):97–102.  https://doi.org/10.1038/pr.2015.56 CrossRefPubMedGoogle Scholar
  41. 41.
    Ishido N, Inoue N, Watanabe M, Hidaka Y, Iwatani Y (2015) The relationship between skewed X chromosome inactivation and the prognosis of Graves’ and Hashimoto’s diseases. Thyroid 25(2):256–261.  https://doi.org/10.1089/thy.2014.0318 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kim JW, Kim HJ (1993)Charcot-Marie-Tooth neuropathy X type 5. In: Adam MP, Ardinger HH, Pagon RA et al (eds) GeneReviews((R)). University of Washington, Seattle University of Washington, Seattle GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved., Seattle (WA)Google Scholar
  43. 43.
    Allred SC, Weck KE, Gasim A, Mottl AK (2015) Phenotypic heterogeneity in females with X-linked Alport syndrome. Clin Nephrol 84(5):296–300.  https://doi.org/10.5414/cn108561 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Bolduc V, Chagnon P, Provost S, Dube MP, Belisle C, Gingras M, Mollica L, Busque L (2008) No evidence that skewing of X chromosome inactivation patterns is transmitted to offspring in humans. J Clin Investig 118(1):333–341.  https://doi.org/10.1172/jci33166 CrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Bo-Yun Yang
    • 1
  • Han-Xiao Yu
    • 2
  • Jie Min
    • 3
  • Xiao-Xiao Song
    • 4
    Email author
  1. 1.Department of Allergy, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Clinical Research Center, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  3. 3.Department of Radiology, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  4. 4.Department of Endocrinology and Metabolism, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina

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