Showing papers by "Philippe Lesavre published in 2006"
TL;DR: Constitutional or acquired dysregulation of the CAP is probably associated with a wide spectrum of diseases, ranging from HUS to glomerulonephritis C3 with MPGN.
Abstract: Introduction: Abnormal control of the complement alternative pathway (CAP) (factor H, factor I and membrane cofactor protein (MCP) deficiencies) is a well established risk factor for the occurrence of haemolytic uraemic syndrome (HUS). In some instances, HUS may be associated with an unusual glomerulonephritis with isolated C3 deposits (glomerulonephritis C3). We determined whether HUS and glomerulonephritis C3 share common genetic susceptibility factors. Methods: We identified 19 patients with glomerulonephritis C3. We measured levels of circulating complement components, performed assays for the detection of C3 nephritic factor (C3NeF) and screened factor H, factor I and MCP coding genes for the presence of mutations. Results: Patients were divided in two groups based on renal pathology findings: group I (n = 13) had typical features of type I membranoproliferative glomerulonephritis (glomerulonephritis C3 with membranoproliferative glomerulonephritis (MPGN)) and group II (n = 6) was characterised by mesangial and epimembranous C3 deposits in the absence of mesangial proliferation (glomerulonephritis C3 without MPGN). Mutations in complement regulatory genes were detected in 4/6 patients with glomerulonephritis C3 without MPGN (heterozygous mutations in factor H gene (two patients) with low factor H antigenic level in one case, heterozygous mutations in factor I gene (two patients)) and in only 2/13 patients with glomerulonephritis C3 with MPGN (heterozygous mutations in factor H gene (one patient) and double heterozygous mutation in CD 46 gene (one patient)). In contrast, C3NeF was present in 5/13 patients with glomerulonephritis C3 with MPGN and in 2/6 patients with glomerulonephritis C3 without MPGN, one of whom had a factor H mutation. Conclusion: HUS and glomerulonephritis C3 without MPGN share common genetic risk factors. Constitutional or acquired dysregulation of the CAP is probably associated with a wide spectrum of diseases, ranging from HUS to glomerulonephritis C3 with MPGN.
260 citations
TL;DR: Nephronophthisis is an autosomal recessivenephropathy with chronic tubulointerstitial involve-ment which represents the leading cause of end-stagerenal disease (ESRD) in children and adolescents and to date, four genes implicated in juvenile or adolescent forms of NPH have been identified.
Abstract: Nephronophthisis (NPH) is an autosomal recessivenephropathy with chronic tubulointerstitial involve-ment, which represents the leading cause of end-stagerenal disease (ESRD) in children and adolescents.According to the age at onset of ESRD, three forms ofNPH have been described: infantile, juvenile (the mostfrequent) and adolescent.In the juvenile form, polyuro-polydipsia starts at4–6 years, and precedes progressive renal failure, withESRD occurring around 13 years of age [1]. Mainhistological findings are tubular atrophy with irregu-larly thickened tubular basement membranes appear-ing at an early stage, interstitial fibrosis and cysts atthe corticomedullary junction and in the medulla [2].The clinical and histological presentation is similar inthe adolescent form, with a later occurrence of ESRD(median age: 19 years). Extra-renal disorders may bepresent in the juvenile form of NPH and includemainly retinal impairment of variable severity. Theclinical and histological features of the infantile formdiffer sharply from the two others: ESRD occurs in thefirst 2 years of life, and patients usually present withenlarged kidneys and widespread cyst development[2,3]. To date, four genes implicated in juvenile oradolescent forms of NPH have been identified:NPHP1, NPHP3, NPHP4 and NPHP5. The mostfrequent genetic abnormality found in NPH is a largehomozygous deletion of the NPHP1 gene [4,5]. Thesefour genes encode proteins named nephrocystins,which have various subcellular localization, includingthe primary apical cilia, focal adhesion and adherensjunction, suggesting that they play a role in theintegrity and architecture of renal tubular epithelialcells [6]. NPHP3 mutations are responsible for theadolescent form of NPH. However, mutations in thefive known genes are found in only 50–60% of NPHcases, indicating that other genes remain to bediscovered [7].NPH is a very rare cause of ESRD in adults. Wereport four cases of NPH diagnosed in adulthood, inwhich molecular study revealed homozygous deletionof NPHP1 gene.
34 citations