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Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis

Nature Genetics volume 44, pages 254–256 (2012)Cite this article

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Abstract

Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC.

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Figure 1: Mutations of SLC20A2 in IBGC.

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References

  1. Manyam, B.V. Parkinsonism Relat. Disord. 11, 73–80 (2005).

    Article  PubMed  Google Scholar 

  2. Miklossy, J. et al. Acta Neuropathol. 109, 643–653 (2005).

    Article  PubMed  Google Scholar 

  3. Wider, C., Dickson, D.W., Schweitzer, K.J., Broderick, D.F. & Wszolek, Z.K. J. Neurol. 256, 839–842 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Oliveira, J.R. et al. Neurology 63, 2165–2167 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Dai, X. et al. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B, 1305–1310 (2010).

    Article  PubMed  Google Scholar 

  6. Bottger, P. & Pedersen, L. J. Biol. Chem. 277, 42741–42747 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Ravera, S., Virkki, L.V., Murer, H. & Forster, I.C. Am. J. Physiol. Cell Physiol. 293, C606–C620 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Prié, D. & Friedlander, G. N. Engl. J. Med. 362, 2399–2409 (2010).

    Article  PubMed  Google Scholar 

  9. Villa-Bellosta, R. et al. Am. J. Physiol. Renal Physiol. 296, F691–F699 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. Kavanaugh, M.P. & Kabat, D. Kidney Int. 49, 959–963 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Kendrick, J., Kestenbaum, B. & Chonchol, M. Adv. Chronic Kidney Dis. 18, 113–119 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Giachelli, C.M. Kidney Int. 75, 890–897 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lagrue, E. et al. J. Biomed. Sci. 17, 91 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rutsch, F. et al. Nat. Genet. 34, 379–381 (2003).

    Article  CAS  PubMed  Google Scholar 

  15. St. Hilaire, C. et al. N. Engl. J. Med. 364, 432–442 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank all the family members for their enthusiastic participation in the study. X.Z. would like to thank K. Hong, Q. Liu, Z. Wu, W. Xia, C. Zhang and L. Zou for clinical support. J.R.M.d.O. would like to thank R. Lemos and D. Oliveira for technical support. This study was mainly supported by the National Natural Science Foundation of China (30670736 and 30972655 to J.-Y.L. and 30730097 and 31021091 to X.Z.) and by the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT; IRT1006 to X.Z.). I.C.F. is supported by the Swiss National Science Foundation. M.L. is supported by the National Natural Science Foundation of China (30871386). J.R.M.d.O. is supported by the John Simon Guggenheim Memorial Foundation and by Conselho Nacional de Desenvolvimento Científico e Tecnológico M.-J.S. and B.Q. are supported by research contracts from the Institute of Health Carlos III and by FEDER funds. The study was approved by the ethics committees of HUST and Peking Union Medical College. Written informed consent was obtained from all participants or their legal guardians.

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Author notes

  1. Cheng Wang, Yulei Li and Lei Shi: These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology (HUST), Wuhan, China

    Cheng Wang, Yulei Li, Jie Ren, Xiaoniu Cui, Xiang-Yang Zhang, Jing Yao, Xiaohua Dai, Juan Liu, Lu Zhang, Hongying Ma, Yong Gao, Xixiang Ma, Shenglei Feng, Mugen Liu, Qing K Wang & Jing-Yu Liu

  2. McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Lei Shi, Lianqing Wang & Xue Zhang

  3. Institute of Physiology, Zurich Center for Integrated Human Physiology, University of Zurich, Zurich, Switzerland

    Monica Patti & Ian C Forster

  4. Department of Neurology, Union Hospital of HUST, Wuhan, China

    Tao Wang

  5. Department of Neuropsychiatry, Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil

    João R M de Oliveira

  6. Fundación Pública Galega de Medicina Xenómica, Clinical Hospital of Santiago de Compostela, Servicio Galego de Saúde (SERGAS), Santiago de Compostela, Spain

    María-Jesús Sobrido & Beatriz Quintáns

  7. Center for Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain

    María-Jesús Sobrido & Beatriz Quintáns

  8. Department of Medicine, University of València, Servei de Neurologia, Hospital Universitari i Politècnic La Fe, València, Spain

    Miguel Baquero

  9. Department of Radiology, Union Hospital of HUST, Wuhan, China

    Haibo Xu

  10. Department of Clinical Laboratory, Hospital of HUST, Wuhan, China

    Junhan Wang

Authors
  1. Cheng Wang
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  2. Yulei Li
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  3. Lei Shi
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  4. Jie Ren
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  5. Monica Patti
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  6. Tao Wang
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  7. João R M de Oliveira
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  8. María-Jesús Sobrido
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  18. Juan Liu
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  19. Lu Zhang
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  20. Hongying Ma
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  21. Yong Gao
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  25. Qing K Wang
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  27. Xue Zhang
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  28. Jing-Yu Liu
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Contributions

J.-Y.L. conceived the study. J.-Y.L. and X.Z. designed the experiments, obtained financial support and wrote the paper. The group of J.-Y.L. discovered the first SLC20A2 mutation. X.Z. coordinated the subsequent international collaboration. C.W., Y.L., L.S. and J.R. carried out the linkage analysis and SLC20A2 mutation screening. L.S., L.W., C.W. and X.-Y.Z. were responsible for molecular cloning. M.P. and I.C.F. conducted 32Pi transport assays. Y.L. performed the bioinformatics analysis. T.W., J.R.M.d.O., M.-J.S., B.Q., M.B., H.X. and J.W. were responsible for clinical evaluation and sample collection. X.C., X.D., J.Y., J.L., L.Z., H.M., Y.G., X.M. and S.F. carried out mutation screening for other candidate genes. M.L. and Q.K.W. supported the genetic analyses.

Corresponding authors

Correspondence to Xue Zhang or Jing-Yu Liu.

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Competing interests

J.Y.L., X.Z., C.W., Y.L., L.S. and J.R. have filed a patent application related to the SLC20A2 sequences and variants. The patent application was filed with the Sate Intellectual Property Office (SIPO) of the People's Republic of China via the Patent Center of the Huazhong University of Science and Technology (HUST).

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Supplementary Methods, Supplementary Figures 1–5 and Supplementary Tables 1–5 (PDF 2415 kb)

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Wang, C., Li, Y., Shi, L. et al. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet 44, 254–256 (2012). https://doi.org/10.1038/ng.1077

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