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Characteristics of the genotype and phenotype in Chinese primary hyperoxaluria type 1 populations

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Abstract

The aim of our study is to explore the relationship between genotype and phenotype in Chinese PH1 patients and determine the putative mutation hotspot regions. This was a retrospective study regarding 13 Chinese PH1 patients. And all sporadic published researches of Chinese PH1 populations were searched and enrolled based on the inclusive standard. All patients presented with multiple urolithiasis or nephrolithiasis. Urinary oxalate values demonstrated an obvious and extensive variability, ranging from 1.01 to 3.85 mmol/1.73 m2. Molecular diagnosis showed that 13 mutant types were detected. Infantile form patient (pt.) 10 and five patients (pts. 5, 7, 8, 9, 12) carrying c.815_816insGA or c.33_34insC demonstrated a worse prognosis, of whom pt. 5 progressed into ESRD 4 years later and died of chronic kidney failure. Based on the integrated Chinese mutation data, two variants (c.815_816insGA and c.33_34insC) were determined as the most common mutations. Besides, c.1049G>A was initially identified in a Chinese patient. Conclusions: heterogeneity between genotype and phenotype was observed and described in Chinese PH1 patients. c.815_816insGA and c.33_34insC which were recognized as AGXT mutation hotspot regions in China implied a poor prognosis. And c.1049G>A was not determined as the race-specific mutation of Pakistani.

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References

  1. Cochat P, Liutkus A, Fargue S, Basmaison O, Ranchin B, Rolland MO (2006) Primary hyperoxaluria type 1: still challenging! Pediatr Nephrol 21:1075–1081. https://doi.org/10.1007/s00467-006-0124-4

    Article  PubMed  Google Scholar 

  2. Leumann E, Hoppe B (2005) Primary hyperoxaluria type 1: is genotyping clinically helpful? Pediatr Nephrol 20:555–557. https://doi.org/10.1007/s00467-005-1813-0

    Article  PubMed  Google Scholar 

  3. Amoroso A, Pirulli D, Florian F, Puzzer D, Boniotto M, Crovella S, Zezlina S, Spanò A, Mazzola G, Savoldi S, Ferrettini C, Berutti S, Petrarulo M, Marangella M (2001) AGXT gene mutations and their influence on clinical heterogeneity of type 1 primary hyperoxaluria. J Am Soc Nephrol 12:2072–2079

    CAS  PubMed  Google Scholar 

  4. Dindo M, Conter C, Oppici E, Ceccarelli V, Marinucci L, Cellini B (2019) Molecular basis of primary hyperoxaluria: clues to innovative treatments. Urolithiasis 47:67–78. https://doi.org/10.1007/s00240-018-1089-z

    Article  CAS  PubMed  Google Scholar 

  5. Beck BB, Hoyer-Kuhn H, Göbel H, Habbig S, Hoppe B (2013) Hyperoxaluria and systemic oxalosis: an update on current therapy and future directions. Expert Opin Investig Drugs 22:117–129. https://doi.org/10.1517/13543784.2013.741587

    Article  CAS  PubMed  Google Scholar 

  6. Strauss SB, Waltuch T, Bivin W, Kaskel F, Levin TL (2017) Primary hyperoxaluria: spectrum of clinical and imaging findings. Pediatr Radiol 47:96–103. https://doi.org/10.1007/s00247-016-3723-7

    Article  PubMed  Google Scholar 

  7. Coulter-Mackie MB (2005) Preliminary evidence for ethnic differences in primary hyperoxaluria type 1 genotype. Am J Nephrol 25:264–268. https://doi.org/10.1159/000086356

    Article  PubMed  Google Scholar 

  8. Coulter-Mackie MB, Lian Q, Applegarth D, Toone J (2005) The major allele of the alanine:glyoxylate aminotransferase gene: nine novel mutations and polymorphisms associated with primary hyperoxaluria type 1. Mol Genet Metab 86:172–178. https://doi.org/10.1016/j.ymgme.2005.05.005

    Article  CAS  PubMed  Google Scholar 

  9. Du D-F, Li Q-Q, Chen C, Shi S-M, Zhao Y-Y, Jiang J-P, Wang D-W, Guo H, Zhang W-J, Chen Z-S (2018) Updated genetic testing of primary hyperoxaluria type 1 in a Chinese population: results from a single center study and a systematic review. Curr Med Sci 38:749–757. https://doi.org/10.1007/s11596-018-1941-y

    Article  CAS  PubMed  Google Scholar 

  10. Work DF, Schwartz GJ (2008) Estimating and measuring glomerular filtration rate in children. Curr Opin Nephrol Hypertens 17:320–325. https://doi.org/10.1097/MNH.0b013e3282fb77f2

    Article  PubMed  Google Scholar 

  11. Cochat P, Hulton S-A, Acquaviva C, Danpure CJ, Daudon M, De Marchi M, Fargue S, Groothoff J, Harambat J, Hoppe B, Jamieson NV, Kemper MJ, Mandrile G, Marangella M, Picca S, Rumsby G, Salido E, Straub M, van Woerden CS, OxalEurope, (2012) Primary hyperoxaluria type 1: indications for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant 27:1729–1736. https://doi.org/10.1093/ndt/gfs078

    Article  CAS  PubMed  Google Scholar 

  12. Amendola LM, Jarvik GP, Leo MC, McLaughlin HM, Akkari Y, Amaral MD, Berg JS, Biswas S, Bowling KM, Conlin LK, Cooper GM, Dorschner MO, Dulik MC, Ghazani AA, Ghosh R, Green RC, Hart R, Horton C, Johnston JJ, Lebo MS, Milosavljevic A, Ou J, Pak CM, Patel RY, Punj S, Richards CS, Salama J, Strande NT, Yang Y, Plon SE, Biesecker LG, Rehm HL (2016) Performance of ACMG-AMP variant-interpretation guidelines among nine laboratories in the clinical sequencing exploratory research consortium. Am J Hum Genet 98:1067–1076. https://doi.org/10.1016/j.ajhg.2016.03.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li X, Gu J, Yang Y, Li J, Li Y (2018) A putative mutation hotspot of the AGXT gene associated with primary hyperoxaluria type 1 in the Chinese population Tohoku. J Exp Med 246:233–241. https://doi.org/10.1620/tjem.246.233

    Article  CAS  Google Scholar 

  14. Lu X, Chen W, Li L, Zhu X, Huang C, Liu S, Yang Y, Zhao Y (2019) Two novel AGXT mutations cause the infantile form of primary hyperoxaluria type I in a Chinese family: research on missed mutation. Front Pharmacol 10:85–85. https://doi.org/10.3389/fphar.2019.00085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li G-m, Xu H, Shen Q, Gong Y-n, Fang X-y, Sun L, Liu H-m, An Y (2014) Mutational analysis of AGXT in two Chinese families with primary hyperoxaluria type 1. BMC Nephrol 15:92–92. https://doi.org/10.1186/1471-2369-15-92

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang C, Lu J, Lang Y, Liu T, Wang X, Zhao X, Shao L (2016) Two novel AGXT mutations identified in primary hyperoxaluria type-1 and distinct morphological and structural difference in kidney stones. Sci Rep 6:33652–33652. https://doi.org/10.1038/srep33652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yuen Y-P, Lai C-K, Tong GM-W, Wong P-N, Wong FK-M, Mak S-K, Lo K-Y, Wong AK-M, Tong S-F, Chan Y-W, Lam C-W (2004) Novel mutations of the AGXT gene causing primary hyperoxaluria type 1. J Nephrol 17:436–440

    CAS  PubMed  Google Scholar 

  18. Coulter-Mackie MB, Lian Q, Applegarth DA, Toone J, Waters PJ, Vallance H (2008) Mutation-based diagnostic testing for primary hyperoxaluria type 1: survey of results. Clin Biochem 41:598–602. https://doi.org/10.1016/j.clinbiochem.2008.01.018

    Article  CAS  PubMed  Google Scholar 

  19. Clifford-Mobley O, Sjögren A, Lindner E, Rumsby G (2016) Urine oxalate biological variation in patients with primary hyperoxaluria. Urolithiasis 44:333–337. https://doi.org/10.1007/s00240-016-0860-2

    Article  CAS  PubMed  Google Scholar 

  20. Jellouli M, Ferjani M, Abidi K, Zarrouk C, Naija O, Abdelmoula J, Gargah T (2016) Primary hyperoxaluria in infants. Saudi J Kidney Dis Transpl 27:526–532. https://doi.org/10.4103/1319-2442.182389

    Article  PubMed  Google Scholar 

  21. Al Riyami MS, Al Ghaithi B, Al Hashmi N, Al Kalbani N (2015) Primary hyperoxaluria type 1 in 18 children: genotyping and outcome. Int J Nephrol 2015:634175–634175. https://doi.org/10.1155/2015/634175

    Article  PubMed  PubMed Central  Google Scholar 

  22. van Woerden CS, Groothoff JW, Wanders RJA, Davin J-C, Wijburg FA (2003) Primary hyperoxaluria type 1 in The Netherlands: prevalence and outcome. Nephrol Dial Transplant 18:273–279. https://doi.org/10.1093/ndt/18.2.273

    Article  PubMed  Google Scholar 

  23. Monico CG, Rossetti S, Schwanz HA, Olson JB, Lundquist PA, Dawson DB, Harris PC, Milliner DS (2007) Comprehensive mutation screening in 55 probands with type 1 primary hyperoxaluria shows feasibility of a gene-based diagnosis. J Am Soc Nephrol 18:1905–1914. https://doi.org/10.1681/ASN.2006111230

    Article  CAS  PubMed  Google Scholar 

  24. Coulter-Mackie MB, Rumsby G (2004) Genetic heterogeneity in primary hyperoxaluria type 1: impact on diagnosis. Mol Genet Metab 83:38–46. https://doi.org/10.1016/j.ymgme.2004.08.009

    Article  CAS  PubMed  Google Scholar 

  25. Mbarek IB, Mdimeg S, Moussa A, Zellama D, Kaarout H, Abdelmoula J, Achour A, Abroug S, Omezzine A, Bouslama A (2017) Unusual clinical outcome of primary Hyperoxaluria type 1 in Tunisian patients carrying 33_34InsC mutation. BMC Nephrol 18:195–195. https://doi.org/10.1186/s12882-017-0612-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Williams E, Rumsby G (2007) Selected exonic sequencing of the AGXT gene provides a genetic diagnosis in 50% of patients with primary hyperoxaluria type 1. Clin Chem 53:1216–1221. https://doi.org/10.1373/clinchem.2006.084434

    Article  CAS  PubMed  Google Scholar 

  27. Kawai C, Minatogawa Y, Akiyoshi H, Hirose S, Suehiro T, Tone S (2012) A novel mutation of human liver alanine:glyoxylate aminotransferase causes primary hyperoxaluria type 1: immunohistochemical quantification and subcellular distribution. Acta Histochem Cytochem 45:121–129. https://doi.org/10.1267/ahc.11042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sas DJ, Harris PC, Milliner DS (2019) Recent advances in the identification and management of inherited hyperoxalurias. Urolithiasis 47:79–89. https://doi.org/10.1007/s00240-018-1093-3

    Article  PubMed  Google Scholar 

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Funding

This study was funded by Beijing Municipal Administration of Hospitals Clinical Medicine Development of special funding support, code: XMLX201826.

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Authors and Affiliations

  1. Department of Urology, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, 100050, China

    Fangzhou Zhao, Jun Li, Lei Tang, Chunming Li, Wenying Wang & Chen Ning

Authors
  1. Fangzhou Zhao
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  2. Jun Li
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  3. Lei Tang
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  4. Chunming Li
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  5. Wenying Wang
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  6. Chen Ning
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Fangzhou Zhao, Lei Tang and Chunming Li, Wenying Wang and Chen Ning. The first draft of the manuscript was written by Fangzhou Zhao and all authors commented on previous versions of the manuscript. Fangzhou Zhao, Wenying Wang and Chen Ning revised this manuscript together. All authors read and approved the final manuscript.

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Correspondence to Jun Li.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zhao, F., Li, J., Tang, L. et al. Characteristics of the genotype and phenotype in Chinese primary hyperoxaluria type 1 populations. Urolithiasis 49, 17–25 (2021). https://doi.org/10.1007/s00240-020-01201-x

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  • DOI: https://doi.org/10.1007/s00240-020-01201-x

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