Pediatric Nephrology

, Volume 28, Issue 2, pp 339–343 | Cite as

Novel INF2 mutation p. L77P in a family with glomerulopathy and Charcot-Marie-Tooth neuropathy

  • Patricia Q. Rodriguez
  • Bernhard Lohkamp
  • Gianni Celsi
  • Christoph Johannes Mache
  • Michaela Auer-Grumbach
  • Annika Wernerson
  • Nobuyuki Hamajima
  • Karl Tryggvason
  • Jaakko Patrakka
Brief Report

Abstract

Background

Mutations in inverted formin, FH2, and WH2 domain containing (INF2) are common causes of dominant focal segmental glomerulosclerosis. INF2 encodes a member of the diaphanous-related formin family, which regulates actin and microtubule cytoskeletons. Charcot-Marie-Tooth neuropathy (CMT) is a group of inherited disorders affecting peripheral neurons. Many reports have shown that glomerulopathy can associate with CMT. However, it has been unclear whether these two processes in the same individual represent one disorder or if they are two separate diseases.

Case diagnosis/treatment

Recently, INF2 mutations were identified in 12 of 16 patients with CMT-associated glomerulopathy, suggesting that these mutations are a common cause of the dual phenotype. In this study, we report two cases of CMT-associated glomerulopathy that both showed INF2 mutations. A novel INF2 mutation, p. L77P, was identified in a family in which the dual phenotype was inherited in a dominant fashion. The pathogenic effect of p. L77P was proposed using a structural homology model. In addition, we identified a patient with a sporadic CMT-associated glomerulopathy carrying a known INF2 mutation: p. L128P.

Conclusions

Our study confirms the link between INF2 mutations and CMT-associated glomerulopathy and widens the spectrum of pathogenic mutations.

Keywords

INF2 FSGS Charcot-marie-tooth disease 

Supplementary material

467_2012_2299_MOESM1_ESM.docx (25 kb)
Supplementary Table 1(DOCX 24.7 kb)

References

  1. 1.
    Patrakka J, Tryggvason K (2009) New insights into the role of podocytes in proteinuria. Nat Rev Nephrol 5:463–468PubMedCrossRefGoogle Scholar
  2. 2.
    Brown EJ, Schlondorff JS, Becker DJ, Tsukaguchi H, Tonna SJ, Uscinski AL, Higgs HN, Henderson JM, Pollak MR (2010) Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Nature Genet 42:72–76PubMedCrossRefGoogle Scholar
  3. 3.
    Boyer O, Benoit G, Gribouval O, Nevo F, Tete MJ, Dantal J, Gilbert-Dussardier B, Touchard G, Karras A, Presne C, Grunfeld JP, Legendre C, Joly D, Rieu P, Mohsin N, Hannedouche T, Moal V, Gubler MC, Broutin I, Mollet G, Antignac C (2011) Mutations in INF2 are a major cause of autosomal dominant focal segmental glomerulosclerosis. J Am Soc Nephrol 22:239–245PubMedCrossRefGoogle Scholar
  4. 4.
    Gbadegesin RA, Lavin PJ, Hall G, Bartkowiak B, Homstad A, Jiang R, Wu G, Bryd A, Lynn K, Wolfish N, Ottati C, Stevens P, Howell D, Conlon P, Winn MP (2011) Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis. Kidney Int 81:94–99PubMedCrossRefGoogle Scholar
  5. 5.
    Lee HK, Han KH, Jung YH, Kang HG, Moon KC, Ha IS, Choi Y, Cheong HI (2011) Variable renal phenotype in a family with an INF2 mutation. Pediatr Nephrol 26(1):73–76PubMedCrossRefGoogle Scholar
  6. 6.
    Patzko A, Shy ME (2011) Update on Charcot-Marie-Tooth disease. Curr Neurol Neurosci Rep 11:78–88PubMedCrossRefGoogle Scholar
  7. 7.
    Paul MD, Fernandez D, Pryse-Phillips W, Gault MH (1990) Charcot-Marie-Tooth disease and nephropathy in a mother and daughter with a review of the literature. Nephron 54:80–85PubMedCrossRefGoogle Scholar
  8. 8.
    Hara M, Ichida F, Higuchi A, Tanizawa T, Okada T (1984) Nephropathy associated with Charcot-Marie-Tooth disease. Int J Pediatr Nephrol 5:99–102PubMedGoogle Scholar
  9. 9.
    Lemieux G, Neemeh JA (1967) Charcot-Marie-Tooth disease and nephritis. Can Med Assoc J 97:1193–1198PubMedGoogle Scholar
  10. 10.
    Boyer O, Nevo F, Plaisier E, Funalot B, Gribouval O, Benoit G, Cong EH, Arrondel C, Tête MJ, Montjean R, Richard L, Karras A, Pouteil-Noble C, Balafrej L, Bonnardeaux A, Canaud G, Charasse C, Dantal J, Deschenes G, Deteix P, Dubourg O, Petiot P, Pouthier D, Leguern E, Guiochon-Mantel A, Broutin I, Gubler MC, Saunier S, Ronco P, Vallat JM, Alonso MA, Antignac C, Mollet G (2011) INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy. New Engl J Med 365:2377–2388PubMedCrossRefGoogle Scholar
  11. 11.
    Otomo T, Otomo C, Tomchick DR, Machius M, Rosen MK (2005) Structural basis of Rho GTPase-mediated activation of the formin mDia1. Mol Cell 18:273–281PubMedCrossRefGoogle Scholar
  12. 12.
    Kellogg EH, Leaver-Fay A, Baker D (2011) Role of conformational sampling in computing mutation-induced changes in protein structure and stability. Proteins 79:830–838PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2012

Authors and Affiliations

  • Patricia Q. Rodriguez
    • 1
  • Bernhard Lohkamp
    • 2
  • Gianni Celsi
    • 3
  • Christoph Johannes Mache
    • 4
  • Michaela Auer-Grumbach
    • 5
  • Annika Wernerson
    • 6
  • Nobuyuki Hamajima
    • 7
  • Karl Tryggvason
    • 1
  • Jaakko Patrakka
    • 1
  1. 1.Division of Matrix Biology, Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden
  2. 2.Division of Structural Biology, Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden
  3. 3.Uppsala University Children’s HospitalUppsalaSweden
  4. 4.Department of General Pediatrics, University Children’s HospitalMedical University GrazGrazAustria
  5. 5.Division of Endocrinology and Metabolism, Department of Internal MedicineMedical University GrazGrazAustria
  6. 6.Department of Clinical Science, Technology and Intervention, Division of Renal MedicineKarolinska InstitutetStockholmSweden
  7. 7.Department of Preventive MedicineNagoya University Graduate School of MedicineNagoyaJapan

Personalised recommendations