| 1. |
- Rodriguez, Patricia Q., et al.
(author)
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Novel INF2 mutation p. L77P in a family with glomerulopathy and Charcot-Marie-Tooth neuropathy
- 2013
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In: Pediatric nephrology (Berlin, West). - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 28:2, s. 339-343
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Journal article (peer-reviewed)abstract
- 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. 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. Our study confirms the link between INF2 mutations and CMT-associated glomerulopathy and widens the spectrum of pathogenic mutations.
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| 2. |
- Xiao, Zhijie, et al.
(author)
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Wtip- and Gadd45a-Interacting Protein Dendrin Is Not Crucial for the Development or Maintenance of the Glomerular Filtration Barrier
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e83133-
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Journal article (peer-reviewed)abstract
- Glomerular podocyte cells are critical for the function of the renal ultrafiltration barrier. Especially, the highly specialized cell cell junction of podocytes, the slit diaphragm, has a central role in the filtration barrier. This is highlighted by the fact that mutations in molecular components of the slit diaphragm, inclucling nephrin and Cd2-associated protein (Cd2ap), result in proteinuric diseases in man. Dendrin is a poorly characterized cytosalic component of the slit diaphragm in where it interact h nephrin and Cd2ap. Dendrin is highly specific for the podocyte slit diaphragm, suggesting that it has a dedicated role in glomerular filtration barrier. In this study, we have generated a dendrin knockout mouse line and explored the molecular interactions of dendrin. Dendrin-deficient mice were viable, fertile, and had a normal life span. Morphologically, the glomerulogenesis proceeded normally and adult dendrin-deficient mice showed normal glomerular histology. No significant protainuria was observed. Fallowing glomerular injury, lack of dendrin did not affect the severity of the damage or h recovery process. Yeast two-hybrid screen and co-immunoprecipitation experiments showed that dendrin binds to interacting protein (Wtip) and growth arrest and DNA-damage-inducible 45 alpha (Gadd45a). Wtip and Gadd45a mediate gene transcription in the nucleus, suggesting that dendrin may have similar functions in podacytes In line with this, we observed he relocation of dendrin to nucleus in adriamycin nephropathy model. Our results indicate that dendrin is dispensable forth unction of the normal glomerular filtration barrier and that dendrin interacts with Wtip and Gadd45a.
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