Marie Claire Gubler

..These data suggest that polycystins could interact with different partners, at least during kidney development...

..Podocin is a protein associated with the slit diaphragm that interacts with nephrin and CD2-associated protein (CD2AP) within lipid rafts...

..Moreover, the identification of the disease based on precise histological and immunohistological analysis, and the research of the genetic defect, now allow genetic counseling and early prenatal diagnosis...

..The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis...

..Moreover, histological analysis of renal tissue allows to assess the severity of degenerative changes and to evaluate the beneficial impact of enzyme replacement therapy...

..In summary, these data demonstrate that CNS is not a distinct clinical entity in non-Finnish populations but rather a clinically and genetically heterogeneous group of disorders...

..Our results suggest that podocin could serve to anchor directly or indirectly components of the slit diaphragm to the cytoskeleton...

..These findings indicate that heterozygous mutations of LMX1B do not appear to dramatically affect the expression of type IV collagen chains, podocin, or CD2AP in NPS patients...

..The two others (R1165L and S96L) are new mutations, although one of them affects a codon (R1165), found elsewhere to be mutated in Sebastian syndrome...

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..No MKS1 mutations were identified in this series, suggesting that the allelism is restricted to MKS3...

..These results provide novel clues in our understanding of normal glomerular function and early events involved in glomerulosclerosis...

..Ctns(-/-) mice of a mixed 129Sv x C57BL/6 genetic background show elevated renal cystine levels; however, proximal tubulopathy or end-stage renal disease is not observed...

..We therefore hypothesized that INF2 may be responsible for cases of Charcot-Marie-Tooth neuropathy associated with FSGS...

..Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling...

..Therefore, and in accordance with the data reported regarding RPGRIP1L, our results indicate phenotype-genotype correlations, as missense and presumably hypomorphic mutations lead to JBS while all null alleles lead to MKS...

..The identification of the disease on the basis of precise histologic analysis and the research of the genetic defect now allow genetic counseling and early prenatal diagnosis...

..This is the first characterization of the mechanisms underlying loss of renin function in RTD...

..In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported...

..This line of mice, humanized for the alpha3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain...

..This is the first identification to our knowledge of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development...

..In particular, kidney disease in BBS is clinically heterogeneous, but is now recognized as a cardinal feature and a major cause of mortality in BBS...

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..These data identify a fourth locus for MKS (MKS4) and the CEP290 gene as responsible for MKS...

..We show that NPHP3 mutations in both infantile and adolescent nephronophthisis point to a common pathophysiological mechanism despite their different clinical presentations...

..The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis...

..Finally, we provide the basis for a polymerase chain reaction (PCR) assay that accurately identifies female carriers and allows adequate genetic counseling in this population...

..To the best of our knowledge, our first patient represents an unreported fetal diagnosis of papillorenal syndrome, and another example of the impact of oriented fetopathological examination in genetic counseling of the parents...

..Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder...

..The same mutations have been observed in genetically female patients with isolated FSGS. Transmission of the mutation is possible. Frasier mutations have also been reported in children with Denys-Drash syndrome...

..This animal model will prove an invaluable and unique tool for testing emerging therapeutics for cystinosis...

..Based on these results we conclude that while cyclosporin therapy can decrease proteinuria in most patients with AS, it may be associated with nephrotoxicity, thereby precluding its long-term use...

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..In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks...

..In summary, constitutive inactivation of podocin models the complex interactions between maternal and genetically determined factors on the progression of renal disease as a result of nephrotic syndrome in mice...

..Animal models have provided invaluable tools to study the mechanisms leading to progressive deterioration of the glomerular basement membrane and ultimately to renal failure, and to evaluate benefits of potential targeted therapies...

..Therapeutic trials in Alport syndrome nephropathy are underway, following promising preliminary results obtained in rodent and canine models of the disorder...

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..In mice, nephrogenesis is completed 2 weeks after birth, whereas in humans it is completed before birth, at 38 weeks of gestation...

..Less nephrotoxic immunosuppressive protocols may improve mGFR and should be further considered. The kidney histology helps in designing personalized immunosuppression strategies for patients...

..In addition, a complex digenic inheritance has been established in some families. Mutations of the BBS10 gene on chromosome 12q21.2 account for 20% of BBS cases...

..Their absence, however, does not guarantee survival to the neonatal period...

..4050 years) ago. We also identified a common MKS3 splice-site mutation, c.1575+1G>A, in five Pakistani sibships of three unrelated families of Mirpuri origin, with an estimated age-of-mutation of 5 generations (125 years)...

..At this time, the indication for these different approaches, which are not mutually exclusive but complementary, depends on the patient clinical presentation and family history...

..In patients with DDS, small glomeruli were observed...

..Risk factors for developing renal failure have been identified: the occurrence and progressive increase in proteinuria, and the development of a hearing defect...